Test Three - Steroidogenesis, Adrenal & Reproductive Glands

Question 1

A ____________________ is a chemical possessing the steroid nucleus, which is also known as the ____________________________ nucleus.

Answer 1

Steroid

Cyclopentanoperhydrophenanthrene

Question 2

What is another name for the steroid nucleus?

Answer 2

Cyclopentaoperhydrophenanthrene

Question 3

Steroid hormones are not packaged but _____________ and immediately ____________ from cells. In other words, steroid hormones are not stored in cells.

Answer 3

Synthesized

Released

Question 4

Are steroid hormones stored in cells?

Answer 4

No, they are synthesized and immediately released

Question 5

What are steroid hormones derived from?

Answer 5

Cholesterol

Question 6

Where are enzymes that produce steroid hormones from cholesterol located?

Answer 6

Mitochondria

Smooth ER

Question 7

Do steroid hormones travel freely in the blood?

Answer 7

No, they must be bound to carrier proteins

Question 8

Why must steroid hormones be bound to carrier proteins?

Answer 8

Because they are highly hydrophobic

Question 9

In some cases, a steroid is secreted by one cell and converted to an active steroid in the target cell. For example, __________, which is secreted by a gonad, is converted into __________ in the brain.

Answer 9

Androgen

Estrogen

Question 10

Cholesterol is composed of phenanthrene attached to a pentano ring and a side chain.

Answer 10

Question 11

You must be able to draw cyclopentanoperhydrophenanthrene (sterane) and cholesterol. You must also be able to number each carbon.

Answer 11

Question 12

What is this?

Answer 12

Cholesterol

Question 13

How many carbons are in cholesterol?

Answer 13

27 carbons

Question 14

Which three steroid groups have 21 carbons?

Answer 14

Progestins

Glucocorticoids

Mineralocorticoids

Question 15

Which groups of steroids have 19 carbons?

Answer 15

Androgens

Question 16

Which groups of steroid hormones have 18 carbons?

Answer 16

Estrogens

Question 17

Which derivative of cholesterol has 27 carbons?

Answer 17

Vitamin D

Question 18

Which groups of steroid hormones have 24 carbons?

Answer 18

Bile acids

Question 19

There are 5 classes of steroid hormones. What are they?

Answer 19

1. Glucocorticoids
2. Mineralocorticoids
3. Androgens
4. Estrogens
5. Progestins

Question 20

How many carbons does each class of steroid hormones contain?

Answer 20

Glucocorticoids have 21 carbons

Mineralocorticoids have 21 carbons

Androgens have 19 carbons

Estrogens have 18 carbons

Progestins have 21 carbons

Question 21

What is the major role of glucocorticoids like cortisol?

Answer 21

Normal stress response

Utilization of carbohydrates, fats, and proteins

Question 22

What is the major role of the mineralocorticoids, like aldosterone?

Answer 22

Salt and water balance

Question 23

What is the major role of androgens, like testosterone?

Answer 23

Male attributes

Question 24

What is the major role of estrogens, like estradiol?

Answer 24

Female attributes

Question 25

What is the main role of the progestins, like progesterone?

Answer 25

Fertilization Implantation Pregnancy maintenance

Question 26

What is the major cellular site of steroidogenesis for the glucocorticoids (cortisol)?

Answer 26

Zona fasciculata of the adrenal cortex

Question 27

What is the major cellular site of steroidogenesis for the mineralocorticoids (aldosterone)?

Answer 27

Zona glomerulosa of the adrenal cortex Outermost layers of zona fasciculata of the adrenal cortex

Question 28

What is the major cellular site of steroidogenesis of the androgens (testosterone)?

Answer 28

Leydig or interstitial cells of the testis Zona fasciculata and reticularis of the adrenal cortex

Question 29

What is the major cellor site of steroidogensis of the estrogens (estradiol)?

Answer 29

Granulosa cells of the ovary Small amounts in the zona fasciculata and reticularis of the adrenal cortex

Question 30

What is the major site of steroidogenesis of the progestins (progesterone)?

Answer 30

Corpus luteum of the ovary Placenta Small amounts from the adrenal cortex

Question 31

What are the three cellular origins of cholesterol?

Answer 31

1. De novo biosynthesis from acetate 2. Circulating lipoprotein in serum 3. Hydrolysis of cholesterol esters within lipids cells of steroidogenic cells

Question 32

\_\_\_\_\_\_\_\_\_\_\_ cholesterol synthesis refers to making cholesterol from _________ by linking carbon atoms together, but it is not common - only 10 to 15 percent of cholesterol is synthesized this way.

Answer 32

*De novo* Acetate

Question 33

HMG-CoA reductase is the enzyme that catalyzes the ______________ step of *de novo* cholesterol synthesis.

Answer 33

Rate-limiting step

Question 34

What enzyme is the rate-limiting step for the *de novo* synthesis of cholesterol?

Answer 34

HMG-CoA reductase

Question 35

HMG-CoA converts HMG-CoA to \_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 35

Mevalonate

Question 36

What is the primary way to regulate *de novo* synthesis of cholesterol?

Answer 36

By regulating the enzyme HMG-CoA reductase

Question 37

What causes Smith-Lemli-Optiz Syndrome?

Answer 37

Defects in *de novo* synthesis of cholesterol

Question 38

What are the symptoms of Smith-Lemi-Oprtiz Syndrome?

Answer 38

1. Psychomotor and growth retardation ​ 2. Distinct craniofacial features​

Question 39

Smith-Lemli-Optiz is an ____________________ genetic disorder characterized by a defect in *de novo* cholesterol synthesis. Severe cases can result in miscarriage or stillborn birth. It affects mostly _____________________ of _____________ descent.

Answer 39

Autosomal recessive White people European descent

Question 40

How do low-density lipoproteins (LDL) deliver cholesterol to the cell?

Answer 40

1. LDL particles bind LDL receptors and scavanger receptor BI (SRBI), HDL receptors, triggering endocytosis​ 2. The endosome fuses with a lysosome, breaking down the lipoproteins and releasing cholesterol via de-esterification 3. Cholesterol diffuses into cytosol from lysosome​ 4. Free cholesterol is converted back to cholesterol ester via ACAT (**acetyl-CoA-cholesterol acyl transferase**), making the cholesterol less soluble and held in storage cells​

Question 41

What is one way in which HMG-CoA reductase is inhibited?

Answer 41

Lots of free cholesterol in cell - the cell do not need to produce cholesterol *de novo* if excess cholesterol is already present

Question 42

LDL brings cholesterol _______ peripheral tissues while HDL brings cholesterol ______ peripheral tissues.

Answer 42

To From

Question 43

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ ___________ are the preferred form of cholesterol transport in bloodstream and storage in the cytosol; they usually do not contribute to plasma membrane structure​.

Answer 43

Cholesterol esters

Question 44

How are cholesterol esters released?

Answer 44

Hydrolysis

Question 45

What enzyme hydrolyzes cholesterol esters?

Answer 45

Cholesteryl ester hydrolase

Question 46

\_\_\_\_\_\_\_\_\_\_\_\_ ____________ \_\_\_\_\_\_\_\_\_\_\_\_\_ hydrolyzes cholesterol ester, producing free cholesterol and _________ \_\_\_\_\_\_\_\_.

Answer 46

Cholesteryl ester hydrolase Fatty acids

Question 47

In the steroidogenic pathway, cholesterol is converted first to _____________________ by PC450scc or \_\_\_\_11A1.

Answer 47

Pregnenolone CYP11A1

Question 48

Free cholesterol must move to the _____________ for steroidogenesis to occur because the first enzyme in the pathway is found there: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. ## Footnote ​

Answer 48

Mitochondria P450scc

Question 49

P450cc is located within the inner or outer mitochondrial membrane?

Answer 49

Inner

Question 50

What is StAR? ## Footnote ​

Answer 50

StAR is a protein that transports cholesterol from the cytosol across the outer mitochondrial membrane and through the inner membrane space to the inner mitochondrial membrane, where P-450scc is located​

Question 51

What does StAR stand for?

Answer 51

Steroidogenic Acture Regulatory Protein

Question 52

P450scc and StAR together comprise the\_\_\_\_\_\_\_\_\_\_\_\_\_ ______________ step of steroidogenesis​. As such, they are often \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 52

Rate-limiting or rate-determing step Regulated

Question 53

Sterodogenic enzymes can be divided into two subgroups: _____________ \_\_\_\_\_\_\_\_\_\_\_ ___________ (CYPs) and _____________ \_\_\_\_\_\_\_\_\_\_\_ (HSDs).

Answer 53

Cytochrome p450 oxidases Hydroxysteroid dehydrogenases

Question 54

Cytochrome p450 oxidases (CYPs) are steroidogenic enzymes that contain a single _____ group. Most are found in the _____________ \_\_\_\_\_\_\_\_\_\_\_\_\_, but some are also found in the mitochondria. They primarily function in the ________ to metabolize endogenous and exogenous toxins, drugs, xenobiotics, and enivironmental pollutants. There are ____ distinct p450 enzymes involved in steroidogenesis.

Answer 54

Heme Endoplasmic reticulum Liver Six

Question 55

What are the six p450 enzymes involved in steroidogenesis?

Answer 55

1. p450scc 2. p450c11β 3. p450c11AS 4. p450c17 5. p450c21 6. p450arom

Question 56

Hydroxysteroid dehydrogenases (HSDs) have no heme group but require _________ or ___________ as cofactors. Each reaction catalyzed by HSDs can be catalyzed by two or more \_\_\_\_\_\_\_\_\_\_\_. There are two families of HSDs: ______ \_\_\_\_\_ dehydrogenases and aldo-keto \_\_\_\_\_\_\_\_\_\_\_\_

Answer 56

NADH NADPH Isozymes Short-chain dehydrogenases Aldo-keto reductases

Question 57

Cleavage of the cholesterol side chain of cholesterol via P-450scc forms pregnenolone, and the fate of pregnenolone is determined by the presence of _____________ within the cell.

Answer 57

Enzymes

Question 58

There are two primary steroidogenic pathways: _______ and \_\_\_\_\_\_\_\_\_. The pathway taken is often species-specific but usually result in the same products.

Answer 58

Δ5 pathway Δ4 pathway

Question 59

What is the primary difference between the Δ5 and Δ4 pathways?

Answer 59

In the Δ5 pathway, pregnenolone is converted to 17α-hydroxyprenenolone by 17α-hydroxysteroid dehydrogenase while in the Δ4 pathway pregnenolone is converted to progesterone first by 3β-hydroxysteroid dehydrogenase before being converted to 17α-hydroxyprenenolone

Question 60

In the Δ5 pathway, pregnenolone is converted to 17α-\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ by ______________________ while in the Δ4 pathway pregnenolone is converted to _____________ by 3β-hydroxysteroid dehydrogenase before being converted to 17α-hydroxyprenenolone

Answer 60

17α-hydroxypregnenolone 17α-hydroxysteroid dehydrogenase Progesterone

Question 61

In the Δ5 pathway, pregnenolone is converted to 17α-hydroxyprenenolone by 17α-hydroxysteroid dehydrogenase while in the Δ4 pathway pregnenolone is converted to progesterone first by 3β-hydroxysteroid dehydrogenase or ________ before being converted to 17α-hydroxyprenenolone

Answer 61

3 beta-HSD

Question 62

The Δ5 pathway is usually found in \_\_\_\_\_\_\_\_\_\_\_\_\_, rabbits, dogs, and ________ while the Δ4 pathway is usually found in rats, \_\_\_\_\_\_\_, mares, and macaques.

Answer 62

Humans Cows Ferrets

Question 63

Which pathway do humans usually follow?

Answer 63

Δ5 pathway

Question 64

There is ________ \_\_\_\_\_\_\_\_\_\_\_\_ of steroidogenic enzymes within each region of the adrenal cortex.

Answer 64

Differential expression

Question 65

You should be generally familar with these enzymes.

Question 66

Estrane, androstane, and pregnane are steroid nomenclatures that designate the placement of what functional group?

Answer 66

Methyl groups

Question 67

Estrane indicates a basic steroid skeleton with 18 carbons and methyl groups at carbons ____ and \_\_\_\_\_.

Answer 67

13 and 17

Question 68

Androstane indicates a steroid skeleton with 19 carbons and methyl groups on carbons ___ and \_\_\_.

Answer 68

13 and 10

Question 69

Pregnane indicates a basic steroid skeleton with 21 carbons and methyl groups on carbons ____ and ___ with a two-carbon atom side chain attached to carbon \_\_\_\_.

Answer 69

13 and 10 17

Question 70

The adrenal glands are also known as the ________ glands because of their location near the kidneys.

Answer 70

Suprarenal

Question 71

The adrenal glands are heavily \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 71

Vascularized

Question 72

Each adrenal gland is structurally and functionally two endocrine glands​: ____________ and \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 72

Adrenal medulla Adrenal cortex

Question 73

The adrenal medulla is associated with the ___________ nervous system and releases \_\_\_\_\_\_\_\_\_\_\_\_\_. The adrenal cortex makes up most of the gland and releases \_\_\_\_\_\_\_\_\_\_\_.

Answer 73

Sympathetic nervous system Catecholamines Corticosteroids

Question 74

The majority of the adrenal gland is composed of the adrenal cortex (\_\_\_\_\_\_%)​ ## Footnote ​

Answer 74

80 - 90%

Question 75

The adrenal medulla is site of __________ and _________ synthesis​ and is associated with the “\_\_\_\_\_\_\_\_\_\_” response. The adrenal cortex is site of glucocorticoid steroid synthesis and is ssociated with “\_\_\_\_\_" response. ## Footnote ​

Answer 75

Epinephrine Norepinephrine Fight or flight Alarm

Question 76

The cells of the zona glomerulosa or ________ layer of the adrenal cortex are _______ to _______ in shape and arranged in rounded clumps, glomeruli, surrounded by capillaries. The round cell nucleus is ______ stained and the cytoplasm is \_\_\_\_\_\_.

Answer 76

Outermost Cuboidal to columnar Darkly stained Acidophilic

Question 77

The middle zona _________ is the broadest layer and consists of cells that are arranged in ________ cords, surrounded by capillaries. The shapes of the cells are ________ or polygonal with a _______ stained cytoplasm. ______ \_\_\_\_\_\_\_ give the cells a foamy appearance. The nucleus is round and darkly stained.

Answer 77

Zona fasciculata Parallel Cuboidal Poorly stained Lipid droplets

Question 78

The ______ zona reticularis consists of cells arranged in less parallel cords, giving it a _________ pattern. The cells of the zona reticularis are ________ and _______ stained than the ones in zona fasciculata.

Answer 78

Inner Reticular Smaller Darker stained

Question 79

These zones of the adrenal cortex cannot be surgically separated because there is no clear boundary between each of them​. We do not understand the differing __________ of the three zones, but one theory is that progenitor cells located underneath the capsule migrate into the interior. ## Footnote ​

Answer 79

Morphologies

Question 80

The zona glomerulosa produces mineralocorticoids namely \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, the major control mechanism of which is \_\_\_\_\_\_\_-\_\_\_\_\_\_\_\_\_\_\_. The zona fasciculata produces glucocorticoids namely \_\_\_\_\_\_\_\_\_, the major control mechanism of which is \_\_\_\_\_\_\_\_\_\_\_. The zona reticularis produces androgens namely _______________ (DHEA), the major control mechanism of which is unknown but includes \_\_\_\_\_\_.

Answer 80

Aldosterone Renin-angiotensin Cortisol Adrenocorticotropic hormone Dehydroepiandrosterone

Question 81

What does ACTH stand for?

Answer 81

Andrenocorticotropic hormone

Question 82

What does DHEA stand for?

Answer 82

Dehydroepiandrosterone

Question 83

Before puberty and sexual maturity, the zona reticularis is the main source of \_\_\_\_\_\_\_\_, which are thought play central role in \_\_\_\_\_\_\_\_\_\_\_\_\_, which may kickstart puberty

Answer 83

Androgens Andrenarche

Question 84

Edward Calvin Kendall, Tadeus \_\_\_\_\_\_\_\_\_\_\_\_, and Philip Showalter Hench won the Nobel Prize in Physiology or Medicine in 1950 for their discoveries relates to the hormones of the adrenal cortex.

Answer 84

Reichstein

Question 85

What three scientists were awarded the Nobel Prize in 1950 for their work on adrenal hormones?

Answer 85

Edward Calvin Kendall Tadeus Reichstein Philip Showalter Hench

Question 86

Kendall and Reichstein independently isolated and characterized _____________ hormones​ while Hench gave ________ to ameliorate symptoms of rheumatoid arthritis​. ​

Answer 86

Cortical Cortisone

Question 87

Which enzymes does the zona glomerulosa express? ## Footnote ​ ​

Answer 87

Aldosterone synthetase or CYP1182

Question 88

What does aldosterone synthetase or CYP1182 catalyze?

Answer 88

The formation of aldosterone

Question 89

Which enzyme does the zona glomerulosa *not* express?

Answer 89

17α-hydroxylase/17,20 lyase or CYP17

Question 90

The zona fasciculata expresses the enzyme ______________ but not \_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 90

17α-hydroxylase (CYP17) 17,20 lyase (CYP17)

Question 91

Which enzyme does the zona reticularis produce?

Answer 91

17,20 lyase or CYP17

Question 92

What is the primary function of 17,20 lyase (CYP17)?

Answer 92

The production of androgens

Question 93

What is the major function of 17α-hydroxylase?

Answer 93

The formation of corticoids

Question 94

Progesterone, cortisol, and aldosterone have ____ carbons; testosterone has ___ carbons; and estradiol has ____ carbons. As a result, progesterone, cortisol, and aldosterone are structurally similar and can bind each other’s receptors at high enough concentrations; when they bind, they generally function as \_\_\_\_\_\_\_\_.​ ## Footnote ​

Answer 94

21 (C-21) 19 (C-19) 18 (C-18)

Question 95

What functional groups at which carbons are essential for the function of progesterone?

Answer 95

Keto groups at C-3 and C-20

Question 96

Which functional groups are essential for cortisol?

Answer 96

Two hydroxyl groups on C-11 and C-17

Question 97

What functional group is essential for aldosterone functioning?

Answer 97

A hydroxyl group at C-21

Question 98

It is believed that the ___________ receptor evolved first followed by the ______________ receptors.

Answer 98

Estrogen Mineralocorticoid

Question 99

\_\_\_\_\_\_\_\_\_\_\_\_ is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish.

Answer 99

Aldosterone

Question 100

Eustachius – 1560s: adrenal glands first identified and noted​ T. Addison – 1850s: began looking at diseases of the adrenal glands​ Brown-Sequard – 1850s: adrenalectomy​ Walter Cannon – 1925: coined term “homeostasis;” described flight or fight response​ Hans Seyle – 1936: described alarm response​ ​ ​

Question 101

There are three sources of cholesterol for adrenal steroidogenesis: (1) *de novo* synthesis from acetate, where HMG-CoA reductase catalyzes the \_\_\_-\_\_\_\_\_\_\_\_\_ step; (2) circulating lipoproteins in serum; and (3) hydrolysis of chesterol esters stored within lipid droplets and catalyzed by \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 101

Rate-limiting step Cholesterol esterase

Question 102

Over \_\_\_% of adrenal steroidogenic hormones are synthesized from circulating lipoprotines and/or stored cholesterol esters.

Answer 102

80%

Question 103

Which two sources of cholesterol for adrenal steroidogenesis are stimulated by ACTH?

Answer 103

1. Receptors for LDL and HDL are upregulated, enabling the cell to obtain cholesterol from circulating lipoproteins 2. Hydrolysis of cholesterol esters is stimlated

Question 104

We know cholesterol esterase (releases cholesterol from lipid droplets) and import of lipoproteins are stimulated by ACTH, most notably in the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_; the other zones can be stimulated by ACTH but to a lesser extent​ ## Footnote ​ ​

Answer 104

Zona fasciculata

Question 105

Mineralocorticoids are produced in the _________________ and function in the regulation of electrolytes, notably ________ and potassium, which are important in regulation of blood pressure and volume. ____________ is the major mineralocorticoid produced by the adrenal gland, and it acts on the _________ to increase blood levels of ____ by decreasing the ion's excretion from the body and increasing the ion's reabsorption.

Answer 105

Zona glomerulosa Sodium or Na+ Aldosterone Kidneys Na+

Question 106

Sodium is a key electrolyte in the body. Why is it more so than other ions?

Answer 106

Water tends to follow sodium

Question 107

What strimulates aldosterone release from the adrenal cortex?

Answer 107

1. Increase blood K+ 2. Decrease blood Na+ 3. ACTH (stress)

Question 108

What decreases aldosterone secretion?

Answer 108

Atrial natriuretic peptide (ANP)

Question 109

What mechanism controls the release of aldosterone?

Answer 109

The Renin-Angiotensin system

Question 110

What is the functional unit of the Renin-Angiotensin System (RAS)?

Answer 110

The juxtoglomerular cell

Question 111

Where is the juxtoglomerular cell located?

Answer 111

The kidneys

Question 112

What do juxtoglomerular cells secrete?

Answer 112

Renin

Question 113

What does renin do?

Answer 113

Raises blood pressure

Question 114

What cells signal to the juxtoglomerular cells that blood pressure is low?

Answer 114

The macula densa cells

Question 115

How do the macula densa cells determine if blood pressure is low?

Answer 115

They detect low sodium concentrations; low levels of blood will have low levels of sodium, therefore blood pressure will be low

Question 116

What do the macula densa cells secrete when they detect that blood pressure is low?

Answer 116

Prostaglandins

Question 117

\_\_\_\_\_\_\_\_\_ ___________ cells in the distal nephrons of the kidney detect low ____ concentrations, which indicate low blood pressure. In response, they release \_\_\_\_\_\_\_\_\_\_\_\_\_, which are paracrine signals that move to the _______________ cells or the functional units of the Renin-Angiotensin System (RAS). When stimulated, these cells release renin, which ______ blood pressure. Renin does so by traveling to the liver, which produces the pro-hormone \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. Renin cleaves this pro-hormone into angiotensin I (A1). A1 travels to the lungs where it encounters _____________________________________________ (ACE) and is cleaved into angiotensin II (A2), a more potent hormone. A2 has many targets, most notably the adrenal cortex, which releases ________________ in response to A2 binding. This mineralocorticoid causes the distal tubules of the nephrone to reabsorb more ____ and therefore \_\_\_\_\_\_\_\_\_.

Answer 117

Macula densa cells Low Na+ concentrations Prostaglandins Juxtoglomerular cells Raises blood pressure Angiotensinogen Angiotensinogen converting enzyme (ACE) Aldosterone Na+ Water

Question 118

Besides the adrenal gland, what other areas of the body does angiotensin II act upon?

Answer 118

1. Directly cause arteries to constrict and increase cardiac output 2. Directly decrease glomerular filtration rate, leading to water retention 3. Directly increases thirst 4. Stimulates ADH (vasopression) release from the posterior pituitary, which increases aquaporin expression in nephrone collecting duct cells and increases sodium reabsorption in the medulla of the kidney

Question 119

Be sure to refresh your memory of how ADH stimulates aquaporin 2 expression.

Answer 119

Question 120

Besides renin, what else can affect aldosterone release?

Answer 120

Increase potassium or decreased sodium in the blood ACTH release by the anterior pituitary in response to stress Atrial natriuretic peptide (ANP) inhibits release (ANP secreted by heart when blood pressure or volume is increased)

Question 121

In the circulation aldosterone (A) is mainly bound to cortisol-binding globulin (CBG) or \_\_\_\_\_\_\_\_\_. Free aldosterone enters the tubule cells of the kidney and binds to the _________ \_\_\_\_\_\_\_\_. This induces release of a ___________ \_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_\_\_\_\_, dimerization of two MRs and translocation to the nucleus where the dimers bind to a ____________ \_\_\_\_\_\_\_\_\_\_\_\_ ____________ (GRE) on the DNA and, along with other transcription factors, initiates protein synthesis. The aldosterone-induced proteins include factors that regulate the luminal Na+ channel and components of the Na+/K+ ATPase pump.

Answer 121

Albumin Mineralocorticoid receptor (cytosol) Heat shock protein Glucocorticoid response element

Question 122

\_\_\_\_\_\_\_\_\_\_\_\_ cells are modified smooth muscle cells which secrete \_\_\_\_\_\_\_. The macula densa are tubular cells of the thick ascending limb of the loop of Henle which can detect circulating concentrations of \_\_\_\_\_\_\_\_\_\_\_.​ In response to the indicated stimuli renin is secreted and converts ________________ (synthesized in the liver) to \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. Angiotensin-converting enzyme (ACE ) converts ________________ \_\_ to ___ which acts on AT1 receptors in the adrenal cortex (glomerulosa) to stimulate aldosterone secretion. ​

Answer 122

Juxtoglomerular cells Renin Na+ Angiotensinogen Angiotensin I Angiotensin I to II

Question 123

Another graphic

Question 124

The renin/angiotensin system stimulates aldosterone secretion, and angiotensin II potentiates the release of ________________ (ADH) and stimulates thirst. Vasopressin secretion is also directly stimulated by hypothalamic osmoreceptors and volume receptors in the cardiovascular system. __________ is released in response to atrial stretch and also inhibits the synthesis and release of aldosterone, and inhibits renin production and AVP release.

Answer 124

Antidiuretic hormone or vasporessin Atrial natriuretic peptide

Question 125

Where are the glucocorticoids produced?

Answer 125

The zona fasciculata of the adrenal cortex

Question 126

What is the primary glucocorticoid?

Answer 126

Cortisol

Question 127

What are the four functions of cortisol?

Answer 127

1. Maintain blood pressure and cardiovascular function 2. Reduce inflammatory response 3. Maintain blood sugar levels by balancing effects of insulin (stimulates gluconeogenesis) 4. Regulates metabolism of proteins, carbohydrates, and fats

Question 128

Cortisol levels are highest when?

Answer 128

The early morning

Question 129

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ stimulates the hypothalmus to produce corticotropic-releasing hormone (CRH), which travels to the anterior pituitary and binds _________________ that then release adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex and binds receptors on cells in the zona fasciculata, stimulating the activity of _________________ \_\_\_\_\_\_\_\_\_\_\_\_ and ________________ (StAR) that will ultimately lead to increased secretion of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 129

Stress Corticotrophs Cholesterol esterase Steroidogenic acute regulatory protein (StAR) Cortisol

Question 130

Cortisol inhibits stress, the \_\_\_\_\_\_\_\_\_\_\_\_\_, and the ___________ \_\_\_\_\_\_\_\_\_\_.

Answer 130

Hypothalamus Anterior pituitary

Question 131

Cortisol has specific metabolic effects in muscle, liver, and fat cells​. In muscle cells, cortisol stimulates the degradation of _________ into its constitutive amino acids, which can then be utilized to make both glucose and the enzymes required for glucose synthesis in the liver​. In liver cells, cortisol stimulates \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, ultimately leading to increased glycogen stores​. In fat cells, cortisol stimulates the breakdown of fat into _____ \_\_\_\_\_ _____ and \_\_\_\_\_\_\_\_\_\_\_\_, which can also be used by the liver to create more glucose ​ Cortisol also directly decreases glucose uptake in peripheral tissues by inhibiting _______ receptors​. ​

Answer 131

Protein Gluconeogenesis Free fatty acids Glycerol GLUT4

Question 132

Cortisol _____________ glucose intake in ___________ tissues via GLUT4 receptors. It increases glucose production and release from the \_\_\_\_\_\_\_\_\_\_. In this way, cortisol is known as a \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, like epinephrine and glucagon.

Answer 132

Decreases Peripheral Liver Diabetogenic

Question 133

The glucocorticoid receptor (GR) is a nuclear steroid receptor with three main domains: a ligand or steroid binding domain, a ________ \_\_\_\_\_\_\_\_\_domain, and a regulatory or transcriptional domain​. The GR is a ___________ nuclear receptor, and it shares a great deal of homology with other such receptors, including the mineralocorticoid receptor; their homology is greater than \_\_\_\_%, specifically when looking at the DNA binding domain​

Answer 133

Type I nuclear receptor DNA-binding domain 90% homology

Question 134

The glucocorticoid receptor is typically found sequestered in the cytosol by ______ \_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_; when cortisol diffuses across the membrane, it binds GR, causing a __________________ \_\_\_\_\_\_\_\_ in GR that exposes its ____________ \_\_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_. GR bound to cortisol then translocates to the nucleus where it _________ with another activates GR and binds the __________ \_\_\_\_\_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_\_\_\_\_, leading to increased transcription of genes related to glucose synthesis . ​

Answer 134

Heat shock proteins Conformational change Nuclear localization signal Dimerizes Glucocorticoid response element (GRE)

Question 135

Like the androgen and progesterone receptors, but unlike thyroid hormone receptors, unliganded GRs are located in the cytoplasm attached to heat shock proteins (hsp-\_\_, hsp-70 and hsp-\_\_).​ When hormones bind to these receptors hsps are released and, through an \_\_\_\_\_\_-dependent process, the hormone receptor complexes translocate to the nucleus.​ These complexes form homo- or heterodimers and the _____ fingers of their DNA-binding domains slot into the glucocorticoid response elements (GREs) in the DNA helix.​

Answer 135

Hsp 90 Hsp 70 Energy Zinc

Question 136

Be familiar with this figure.

Question 137

Where are the gonadocorticoids produced?

Answer 137

The zona reticularis of the adrenal cortex

Question 138

What is the primary sex hormone produced by the zona reticularis?

Answer 138

Androgens Androstenedione Dehydroepiandrosterone (DHEA)

Question 139

Adrenal androgens are converted to _________ in males and ___________ in females. The exact role for adrenal sex hormones is unknown, but they are believed to contribute to the onset of puberty, secondary sex characteristics, and sex drive in females

Answer 139

Testosterone Estrogen

Question 140

\_\_\_\_\_\_\_\_\_\_\_\_\_\_, a period of high adrenal androgen production, precedes puberty and is believed to lead to puberty (e.g., causes underarm and pubic hair)

Answer 140

Andrenarche

Question 141

We don’t know exact regulatory mechanism of the adrenal androgens, but we do know that ___________ stimulates adrenal androgen production, specifically DHEA and androstenedione.

Answer 141

ACTH

Question 142

DHEA and androstenedione are converted to testosterone via \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. Testosterone can be further converted in males into 5α-dihydrotestosterone (5α-DHT), a more potent androgen, via \_\_\_\_\_\_\_\_\_\_\_\_\_\_. Testosterone can be further converted in females and males into estradiol via \_\_\_\_\_\_\_\_\_.

Answer 142

17β-hydroxysteroid dehydrogenase (17β-HSD) 5α reductase Aromatase

Question 143

Because adrenal androgens are stimulated by ACTH, they mimic ____________ release.

Answer 143

Cortisol

Question 144

Conn’s Syndrome caused by excess _____________ production from a benign tumor of the adrenal gland, likely the __________________ \_\_\_\_\_\_\_\_\_\_\_\_\_. Common symptoms include hypertension and hypoalkaemia or \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 144

Aldosterone Low blood potassium levels

Question 145

What cause secondary aldosterone excess?

Answer 145

Low blood volume, usually due to edema

Question 146

How does edema lead to secondary aldosterone excess?

Answer 146

Low blood volume activates the renin-angiotensin-aldosterone system, ultimately increase aldosterone production; aldosterone will continue to increase blood volume, but blood volume will continue to register as low because fluid pools in the peripheral tissues due to damage in blood vessels

Question 147

What are two disorders of aldosterone excess?

Answer 147

Conn's Syndrome (primary) Secondary

Question 148

Be familar with this figure.

Question 149

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is caused by a mutated gene for CYP21 or \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, which is necessary for the production of aldosterone and \_\_\_\_\_\_\_\_\_\_\_. When the enzyme is defective, intermediates of the steroidogenic pathway are transformed into androgens because the lack of ______________ results in no negative feedback to the hypothalamus and pituitary gland. The lack of negative feedback results in increased _________ and thus steroidogenesis in the adrenal cortex and the upregulation of \_\_\_\_\_\_\_, which converts pregnenolone into DHEA.

Answer 149

Congential adrenal hyperplasia 21β-hydroxylase Cortisol Cortisol CYP17 (17α-hydroxylase, 17,20-lyase)

Question 150

Babies with congenital adrenal hyperplasia are usually born with ambiguous genitalia; the image shown is of a female baby who has developed __________ genitalia because adrenal androgens have been converted into ______________ (DHT). Treatment of CAH is simple: the individual is given exogenous aldosterone and cortisol.

Answer 150

5α-dihydrotestosterone

Question 151

Individuals with congenital adrenal hyperplasia often have severe hypovolemia, hyponatremia, and hyperalkemia. Why does this occur?

Answer 151

CYP21 (21β-Hydroxylase) is mutated, so progestorone can not be converted into the precursors for aldosterone and cortisol. Aldosterone stimulates the kidneys in the Renin-Angiotensin-Aldosterone System (RAAS) to increase Na+ and water absorption. Without aldosterone, then, low blood volume (hypovolemia) and low Na+ (hypoatremia). If there is low Na+ in the blood, the sodium-potassium pump will be dysregulated (usually for every 3 Na+ pumped out of the cell, 2 K+ are pumped inside), thereby resulting in hyperalkemia (high blood K+).

Question 152

Patients with cogenital adrenal hyperplasia often have increased levels of ACTH, 17-OH progesterone, and androgens. Why is this?

Answer 152

CYP21 (21β-Hydroxylase) is defective and cannot transform progesterone into aldosterone precursors or 17-OH progesterone into cortisol precursors. Without cortisol production, there is no negative feedback to the hypothalamus, so ACTH is continuously stimulated. This causes the steroidogenic pathways of the adrenal glands to be continuously stimulated, ultimately leading to more progesterone and 17-OH progesterone and androgens.

Question 153

What are two disorders that result from adrenal hypofunction?

Answer 153

Primary hypofunction (Addison's Disease) Secondary hypofunction

Question 154

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is a disorder characterized by low levels of cortisol (markedly) and aldosterone. In the past, it was due to destruction of the adrenal cortex by \_\_\_\_\_\_\_\_\_\_\_\_, but today, it is most often seen as a result of an __________ disorder. The symptoms of this disease include fatigue, loss of appetite, ____________ weight, hypoglycemia, decreased blood pressure, _________ craving for salty foods, and ____________ pigmentation.

Answer 154

Addison's Disease Tuberculosis Autoimmune disorder Decreased Increased Increased

Question 155

Why do patients with Addison's Disease often have hyperpigmentation?

Answer 155

Low levels of cortisol are unable to engage in negative feedback with the hypothalamus and pituitary gland; therefore, the pituitary gland continues to synthesize POMC or pro-opiomelanocortin, the precursor for ACTH; when POMC is cleaved, ACTH is formed as is melanocyte-stimulating hormone (MSH), which stimulates melanocytes and leads to hyperpigmentation

Question 156

Secondary adrenal hypofunction is not as problematic as primary adrenal hypofunction and is the result of impaired hypothalamic-pituitary-adrenal regulation, notably decreased \_\_\_\_\_\_\_\_\_\_.

Answer 156

ACTH

Question 157

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_'s syndrome is caused by excess cortisol, the most common cause of which is use of glucocorticoids to treat other disorders. A secondary cause is ___________ overproduction that can be either ACTH-dependent (the syndrome) or ACTH-independent. . The syndrome is most often caused by tumors in the adrenal or pituitary glands.

Answer 157

Cushing's syndrome Endogenous (Cushing's is ACTH-dependent)

Question 158

What are the common symptoms of Cushing's Syndrome or hyperadrenocorticisim?

Answer 158

Common symptoms of Cushing's Syndrome include a 1. Redistribution of fat to the abdomen 2. thinning of the limbs (muscle wasting as cortisol causes breakdown of proteins in muscle) 3. buffalo hump 4. Thinning of skin 5. Striations 6. hypertension (mineralocorticoid effects) 7. easy bruising 8. Purpure

Question 159

People with Cushing's Syndrome are at increased risk for diabetes and cardiovascular problems. Why?

Answer 159

Cortisol increases insulin resistance and increases blood glucose levels

Question 160

The adrenal medulla is made up of modified ganglionic sympathetic neurons called ____________ cells. These cells secrete epinephrine and norepinephrine, which are \_\_\_\_\_\_\_\_\_. Secretion of these hormones results in increased blood glucose levels, blood vessel constriction, heart rate, bronchial dilation and oxygen intake, and blood diverted to the \_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_, and skeletal muscle.

Answer 160

Chromaffin Catecholamines Blood, heart

Question 161

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is the primary product of the adrenal medulla.

Answer 161

Epinephrine "fight or flight"

Question 162

Chromaffin cells are clustered with faint basophilic cytoplasm and granules of catecholamines. They are highly _________ and _________ in nature - their products are released directly into circulation.

Answer 162

Vascularized Neurosecretory

Question 163

Catecholamines are _________ derivatives. This amino acid is first transformed into DOPA via __________ \_\_\_\_\_\_\_\_\_\_, which is the rate-limiting step, and then to dopamine via aromatic amine acid decarboxylase, norepinephrine via dopamine β hydroxylase and finally epinephrine via phenylethanolamine N-methyl transferases.

Answer 163

Tyrosine Tyrosine hydroxylase

Question 164

Tyrosine is first converted to DOPA by tyrosine hydroxylase. DOPA is converted to dopamine via __________ \_\_\_\_\_\_\_ ________ decarboxylase (AAD). Dopamine is converted to norepinephrine via dopamine β‐hydroxylase. Norepinephrine is converted to epinephrine via _______________ \_\_\_\_\_\_\_\_\_ ___________ (PNMT).

Answer 164

Aromatic amine acid decarboxylase (AAD) Phenylethanolamine N-methyl transferase

Question 165

Catecholamine synthesis is stimulated by the nervous system. Stress triggers higher brain centers to signal the release of ____________ from the sympathethic nervous system. This neurotransmitter binds ___________ \_\_\_\_\_\_\_\_\_, which then increase secretion of epinephrine and norepinephrine that enter circulation. The catecholamines have _____ half lives. Most are taken back up and reused by the cells that produce them and target cells.

Answer 165

Acetylcholine Chromaffin cells Short half-lives

Question 166

What does each enzyme acronym stand for?

Answer 166

TH = tyrosine hydroxylase AAD = aromatic amin acid decarboxylase DβH = dopamine β‐hydroxylase PNMT = phenylethanolamine N‐methyl transferase

Question 167

·What is the fate of secreted catecholamines?

Answer 167

- reuptake by catechol-secreting cells for reuse or metabolism - uptake by receptors on effector cells - metabolized by inactivating mechanisms, mostly in liver

Question 168

What are the actions of epinephrine?

Answer 168

The response depends on type of adrenergic receptor, but in general, epinephrine causes arousal: alerting, pupillary dilation, piloerection, sweating, bronchiodilation, tachycardia, smooth muscle inhibition in GI, sphincter contraction, relaxation of uterine muscles; increased metabolic actions (glycogenolysis, lipolysis); and increased cardiovascular actions (stimulates HR and vasoconstriction, ↑ BP)

Question 169

Differential localization of adrenergic receptors leads to different cellular responses. Beta1 receptors are localized to the \_\_\_\_\_\_\_. Beta2 receptors are localized to _______ and ________ \_\_\_\_\_\_\_\_\_\_\_ cells. Beta3 receptors are localized to ___________ tissue and \_\_\_\_\_\_\_\_\_\_\_. Alpha receptors are largely but not exclusively localized to the _________ and reproductive system

Answer 169

Heart Smooth and skeletal muscle Adipose tissue and fat GI tract

Question 170

What disorder of the adrenal medulla did we discuss in class?

Answer 170

Pheochromocytomas (benign tumors of the adrenal medulla)

Question 171

What do pheochromocytomas cause?

Answer 171

They cause excess catecholamines and therefore decreased insulin production; hypertension, tachycardia; sweating; tremor, palpitations; nervousness; weight loss; hyperglycemia

Question 172

How are pheochromocytomas diagnosed

Answer 172

Free plasma catecholarime levels Urinary catecholamine metabolite (metaneprhines) CT scan

Question 173

What do pheochromocytomas often present similarly to?

Answer 173

Hyperthyroidism

Question 174

The long-term stress response is also known as the “\_\_\_\_\_\_” system and stimulates the adrenal __________ to produce cortisol and aldosterone. Aldosterone works to increase sodium and water reabsorption in the kidneys and to increase blood volume and blood pressure. Cortisol works to increase glucose levels and to suppress the immune system The short-term stress response is also known as the “\_\_\_\_\_\_\_\_\_\_” system and stimulates the adrenal _________ to produce catecholamines. Catecholamines work to increase heart rate, increase blood pressure, convert glycogen to glucose and increase blood glucose levels, increase bronchiole dilation, decrease digestion and urine production, and increase metabolic rate.

Answer 174

Alarm Adrenal cortex Fight or flight Adrenal medulla

Question 175

What is sexual differentation?

Answer 175

Process by which bipotential gonad develops into testis or ovary which is determined by presence/absence of Y chromosome

Question 176

The ____________ paradigm of sexual differentiation was established via experiments on rabbits; rabbits castrated before development developed into females, thereby establishing female sex as the “default” sex. The paradigm states that the establishment of chromosomal/genetic sex occurs at fertilization, which then influences the development of gonads (gonadal sex) and ultimately external and internal genitalia (phenotypic sex).

Answer 176

Jost

Question 177

What does the Jost paradigm of sexual differentation propose?

Answer 177

The paradigm states that the establishment of chromosomal/genetic sex occurs at fertilization, which then influences the development of gonads (gonadal sex) and ultimately external and internal genitalia (phenotypic sex).

Question 178

How many chromosomes do human somatic cells contain?

Answer 178

46 (including sex chromosomes)

Question 179

Human somatic cells are diploid but gametes are \_\_\_\_\_\_\_\_\_\_.

Answer 179

Haploid

Question 180

The ___________ determines chromosomal sex.

Answer 180

Sperm

Question 181

Females are \_\_\_\_\_\_\_\_\_\_\_\_\_\_; males are heterogametic

Answer 181

Homogametic

Question 182

Humans have an X and Y chromosome, but other species may have different sex chromosomes (e.g., male birds are __ and female birds are \_\_

Answer 182

ZZ ZW

Question 183

The ___ chromosome is the critical determinant of chromosomal and genetic sex

Answer 183

Y chromosome

Question 184

XY or XXY or XXYY or XXXY or XXXXY = \_\_\_\_\_\_ XX or XXX = \_\_\_\_\_\_\_\_\_\_\_ XO = _________ with incomplete ____________ development XXY or XXYY or XXXY or XXXXY = ________ but impaired _________ production

Answer 184

Male (testis) Female (ovary) Female but incomplete ovarian development Male but impaired sperm production

Question 185

How is dosage compensation achieved in females?

Answer 185

X inactivation

Question 186

How does X inactivation occur in women?

Answer 186

X inactivation occurs by condensing one of the two X chromosomes in women; the Barr Body is the heterochromatized X chromosome (i.e., heterochromatin is condensed chromatin where genes are unable to be expressed)

Question 187

The _____ \_\_\_\_\_ is the heterochromatized X chromosome

Answer 187

Barr Body

Question 188

The X chromosome marked for inactivation expresses the _____ gene, a non-protein coding gene that codes for RNA. The mRNA product coats the X chromosome; this coat then recruits chromatin remodeling complexes to the X chromosome, condensing the X chromosome into the Barr Body and leading to dosage compensation. If you increase the number of X chromosomes, you increase the amount of ____ expression The other X chromosome expresses \_\_\_\_\_, which codes for an \_\_\_\_\_\_\_\_\_mRNA that prevents the remodeling of the X chromosome.

Answer 188

XIST XIST TSIX Antisense

Question 189

Once X inactivation occurs, it is reflected or not reflected in remaining cells?

Answer 189

Reflected

Question 190

Alligators do not have sex chromosomes; instead, sex is dependent upon \_\_\_\_\_\_\_\_. At temperatures greater than 34 degrees Celsius, an egg will incubate into a \_\_\_\_\_\_\_. At temperatures lower than 30 degrees Celsius, an egg will incubate into a \_\_\_\_\_\_\_\_. The same is true for turtles, except the temperature restrictions are flipped (high temperatures result in \_\_\_\_\_\_\_\_\_, low temperature result in \_\_\_\_\_\_\_\_\_).

Answer 190

Temperature Males Females Females Males

Question 191

In alligators and turtles, __________ regulates the expression of enzymes necessary for gonad formation and sexual differentiation.

Answer 191

Temperature

Question 192

In other species, sex determination is based on social and behavioral factors (e.g., fish) that stimulate hormonal changes that result in sexual differentiation of phenotype. _________ results when a male changes to female. _________ results when a female changes to male.

Answer 192

Protandry (male to female) Protogyny (female to male)

Question 193

The Y chromosome contains the ______ gene (\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_). This gene produces the __________ \_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_\_.

Answer 193

SRY Sex determining region on the Y chromosome Testis determining factor (TDF)

Question 194

Besides the sex-determining region on the Y chromosome (SRY) gene, which contains the testis-determining factor (TDF), what else is interesting about the Y chromosome?

Answer 194

It is smaller (less than 100 genes). It also contains genes important in skeletal growth and spermatogenesis, and pseudo-autosomal regions are located on the ends of the chromosome so that pairing with the X chromosome can occur

Question 195

The SOX9 gene expresses the SOX9 protein, which regulates skeletal development and sex determination; it is stimulated by the ______ gene (e.g., TDF), fibroblast growth factor 9, and prostaglandin D synthetase, ultimately leading to testis development. In women, SOX9 must be inhibited, usually by \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 195

SRY gene (sex-determining region of the Y chromosome) FOXL2 (forkhead box L2)

Question 196

What does SOX9 stand for?

Answer 196

SRY Box 9

Question 197

What stimulates SOX9?

Answer 197

The SRY gene FGF9 PGDS (prostaglandin D synthetase)

Question 198

What inhibits SOX9?

Answer 198

FOXL2 (forkhead box L2)

Question 199

Activation of SOX9 leads to __________ development.

Answer 199

Testis

Question 200

The mammalian ovary and testis develop from ___________ \_\_\_\_\_\_\_\_\_\_\_\_ gonads.

Answer 200

Bipotential primordial gonads

Question 201

Germ cells move to the _________ \_\_\_\_\_\_\_\_\_ where they form bipotential cells and develop germinal epithelium. If male, the primary sex cords continue to elongate and develop into the seminiferous tubules where sperm will develop, and testosterone will be produced. If female (lack of Y chromosome), the primary sex cords will degenerate, and the secondary sex cords will develop, ultimately forming the ovarian cortex and follicles. Gonads form from the _________ tubules (pre-pre-kidneys)

Answer 201

Genital ridge Mesonephric

Question 202

REMEMBER: THE Y CHROMOSOME and the SRY GENE as well as the testis ARE THE PRIMARY DETERMINANTS OF SEX

Question 203

In males, we see the regression of the Mullerian ducts due to the presence of ____________ hormone, which is expressed specifically in the \_\_\_\_\_\_\_\_; this leaves the male with the _________ ducts that then develop into the ____________ and accessory glands as the testes produce androgens.

Answer 203

Anti-Mullerian hormone (AMH) Testes Wolffian ducts Vas deferens

Question 204

In females, we see the continuation of the _____________ ducts and the degeneration of the _________ \_\_\_\_\_\_\_\_\_ (i.e., there are no androgens present because there are no testes, so these ducts do not continue development); the ________ ducts will continue to develop into the oviducts, uterus, cervix, and the upper part of the vagina.

Answer 204

Mullerian Wolffian ducts Mullerian

Question 205

The development of external genitalia is dependent upon _________ availability. The genital ________ will form either the penis or clitoris. The \_\_\_\_\_\_\_\_folds will form either the underside of the penis (penile \_\_\_\_) or the labia minora. The _________ swellings will form either the scrotum or labia majora.

Answer 205

Hormone Genital tubercle Urogenital folds Penile raphe Labiosacral swellings

Question 206

What are the five steps of internal male development discussed?

Answer 206

1. Organization of testes into spermatogenic cords, containing fetal Sertoli cells and primordial germ cells (~7wks) 2. Regression of müllerian ducts caused by AMH, produced by the fetal Sertoli cells (~8wks) 3. Mesenchymal cells differentiate into Leydig cells which synthesize testosterone (~8-9wks) 4. Male genital tract (epididymis, vas deferens, and seminal vesicles) develops from the Wolffian ducts in response to increased testosterone 5. Prostate gland development begins at ~10wks (and continues even after birth)

Question 207

\_\_\_\_\_\_\_\_\_\_\_\_ cells will produce AMH, leading to the regression of the Mullerian ducts in males \_\_\_\_\_\_\_\_\_ cells will produce testosterone, leading to the elongation of the Wolffian ducts into the epididymis

Answer 207

Sertoli cells Leydig cells

Question 208

Be familiar with this picture

Question 209

What are the three stages of external male development discussed in class?

Answer 209

1. Genital swellings enlarge and migrate posteriorly to form scrotum; genital folds fuse over urethral groove to form penile urethra; prepuce develops to cover glans penis (9‐12th wks) 2. Growth of external genitalia 3. Testicular descent a. Transabdominal phase (10‐15wks) b. Inguinoscrotal phase (26‐35wks)

Question 210

In the _____________ phase, the testes descend, stimulated by \_\_\_\_, which is produced by the testes; the *gubernaculum* swells, which contributes to testes descent, in response to androgen production. The second phase of testicular descent, the ___________ phase, corresponds to the migration of the testes and epididymis through the inguinal canal into the \_\_\_\_\_\_; it is stimulated by _________ produced by the testes.

Answer 210

Transabdominal phase IGF3 Inguinoscrotal phase Scrotum Androgens

Question 211

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is responsible for Wolffian development, spermatogenesis, and gonadotropin regulation while __________________ is responsible for external virilization, prostate development, and pubertal maturation

Answer 211

Testosterone 5α-dihydrotestosterone (DHT)

Question 212

\_\_\_\_\_\_\_\_\_\_\_ converts testosterone to 5α-dihydrotestosterone (DHT), which has a higher affinity for the androgen receptor; DHT is a much __________ androgen and is central to \_\_\_\_\_\_\_\_\_\_\_. In fact, males without this enzyme are unable to transform testosterone into DHT, ultimately leading to the development of a micropenis and \_\_\_\_\_\_\_\_\_\_, where the urethral opening develops on the underside of the penis

Answer 212

5α-reductase Stronger androgen Virilization Hypospadias

Question 213

What are the five stages of internal female development discussed in class?

Answer 213

1. Cortical cords appear in indifferent gonads, and primordial germ cells concentrate along the cords 2. Müllerian ducts form the oviducts, the uterus, cervix, and the upper 1/3 of the vagina. (~10 wks) 3. The Wolffian ducts regress (~10wks) 4. Estrogen is produced by the fetal ovary but is not believed to play a large role in female sexual differentiation 5. Follicular development begins (~15wks)

Question 214

In females, the lack of _________ results in the regression of the ___________ ducts and the lack of __________ results in the persistence of the ___________ ducts

Answer 214

Androgens Wolffian ducts Anti-Mullerian hormone (AMH) Mullerian ducts

Question 215

Be familiar with this figure.

Question 216

We should be able to go through this figure.

Question 217

What are two disorders of chromosal sex discussed in class?

Answer 217

Klinefelter Syndrome (47, XXY) Turner Syndrome (45, XO)

Question 218

\_\_\_\_\_\_\_\_\_\_\_ Syndrome (47, XXY) affects 1/500 newborn males. Before puberty, the testes are ______ and have _________ numbers of spermatogonia. After puberty, incomplete virilization, sterility, and breast enlargement. Patients will usually have low to normal testosterone but increased \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 218

Klinefelter Small Decreased Estradiol

Question 219

\_\_\_\_\_\_\_\_\_\_ Syndrome (45, XO) is rarer than Klinefelter Syndrome. Patients present phenotypically __________ but are often of short statuture and lack menstrual cycles and secondary sexual characteristics. This syndrome is associated with multiple cogenital abnormalities and may present with __________ \_\_\_\_\_\_\_\_ gonads.

Answer 219

Turner Female Bilateral steak gonads

Question 220

Individuals with Turner Syndrome often have a characteristically wide __________ neck.

Answer 220

Webbed

Question 221

What disorder of gonadal sex did we discuss in class?

Answer 221

Gonadal dysgenesis

Question 222

What is gonadal dysgenesis?

Answer 222

Occurs in individuals who are genotypically male or female but abnormal gonadal development

Question 223

Individuals with gonadal dysgenesis (46 XX or XY) will often have bilateral streak gonads and display an immature _________ phenotype since gonadal development is arrested before _________ and ___________ are produced. 46, XY complete gonadal dysgenesis can result from mutations in any number of genes including SRY, Wilms’ Tumor-Related 1, Steroidogenic Factor 1 (SF1), SOX9, and DAX-1.

Answer 223

Female AMH Androgens

Question 224

\_\_\_\_\_\_\_\_\_\_\_\_ is an important gene in steroidogenic pathways; it affects production of androgens and other steroidogenic genes; it can cause defects elsewhere including adrenal gland. SOX9 defects can lead to gonadal dysgenesis and congenital hyperplasia (skeletal development problems).

Answer 224

SF1 (Steroidogenic Factor 1)

Question 225

Be familiar with this figure.

Question 226

What disorders of phenotypic sex did we discuss in class?

Answer 226

Pseudohermaphroditism and hermaphroditisim

Question 227

\_\_\_\_\_\_\_\_\_\_\_\_\_ pseudohermaphroditism possess ovaries and Müllerian derivatives amd have varying degrees of virilization of the external genitalia. It is usually caused by in utero exposure to _________ (ex. Congenital adrenal hyperplasia, placental aromatase deficiency).

Answer 227

Female pseudohermaphroditism Androgens

Question 228

\_\_\_\_\_\_\_ Pseudohermaphroditism results from defects in ________ synthesis in testes, defects in __________ action in target cells, and defects in ____________ duct regression.

Answer 228

Male Androgen Androgen Mullerian

Question 229

Hermaphroditism results when a person has an ambiguous __________ or one that disagrees with genetic and gonadal sex.

Answer 229

Phenotypic sex

Question 230

True hermaphroditism is \_\_\_\_\_\_\_\_\_\_, and patients present with both ovarian and testicular tissue or \_\_\_\_\_\_\_\_\_\_\_\_\_\_. True hermaphroditism can result in an error in fertilization where half the cells are 46:XX and the other are 46:XY; however, most have 46:\_\_\_ karyotypes.

Answer 230

Rare Ovatestis 46:XX

Question 231

What are the three functions of the male reproductive system?

Answer 231

To produce testosterone, male gametes, and sperm (and its delivery)

Question 232

The accessory glands have __________ function.

Answer 232

Exocrine

Question 233

The accessory glands form the ________ in which sperm travels.

Answer 233

Fluid

Question 234

The testes are found inside the scrotum, which hangs below the body and consists of skin and _______________ \_\_\_\_\_\_\_\_\_\_\_\_\_. There is a ____________ that divides the scrotum. Sperm is produced in the tests and then travels to the ______ testis, the epididymises, vas deferens, ejaculatory duct, and finally urethra. The accessory glands include the __________ vesicles, the __________ gland, and the ___________ glands.

Answer 234

Superficial fascia Septum Rete testis Seminal vesicles Prostate gland Bulbourethral gland

Question 235

The testes is surrounded by two protective layers: the outer ___________ \_\_\_\_\_\_\_\_\_\_ and the inner, thicker ____________ \_\_\_\_\_\_\_\_\_\_\_\_\_, which divides the testes into _________ each of which contains between 2 and 4 seminiferous tubules.

Answer 235

Tunica vaginalis Tunica albuginea Lobules

Question 236

The ____ \_\_\_\_\_ is the site in which sperm enters prior to entering the epididymis.

Answer 236

Rete testis

Question 237

The seminiferous tubules extend throughout the testes and are arranged into \_\_\_\_\_\_\_\_\_\_\_\_\_. They are lined with a ______________ membrane. Inside are the Sertoli cells, which nurse developing ____________ cells, and the ___________ cells themselves. Outside are the Leydig cells, which produced androgens, and the __________ cells, responsible for contracting and moving sperm through the seminiferous tubules.

Answer 237

Lobules Basement membrane Sperm cells Sperm cells Myoid cells

Question 238

The testes is vascularized but located outside or inside the seminiferous tubule?

Answer 238

Outside

Question 239

The seminiferous tubules are tightly coiled structures composed of germ cells (developing sperm cells), Sertoli cells, and __________ cells. Their most important function is the production of \_\_\_\_\_\_\_\_\_.

Answer 239

Peritubular tissue Sperm

Question 240

Sertoli cells are held together by __________ junctions near the ________ side of the seminiferous tubules, essentially preventing the movement of any external substances into the seminiferous tubule. These junctions are referred to as the “blood-testis barrier” The Sertoli cells are the functional unit of the seminiferous tubules, and sperm develops in between the Sertoli cells, moving from the basal membrane to the lumenal space

Answer 240

Tight junctions Basal

Question 241

Spermatogenesis refers to the formation of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. As the bipotential gonads are forming, the germ cells move to the genital ridge, and as they do so, they undergo proliferation so that by the time they arrive at the genital ridge, approximately _______ germ cells are present. By the time of \_\_\_\_\_\_\_\_\_\_, cell proliferation results in about 6 million germ cells present; these germ cells are \_\_\_\_\_\_\_\_\_\_\_\_\_. Around puberty, these cells are triggered to begin preparing for meiosis II; they undergo cell growth and DNA replication, transforming into _________ \_\_\_\_\_\_\_\_\_\_\_\_\_, diploid cells, just before entering meiosis I. After the first round of meiosis, the primary spermatocytes are transformed into __________ spermatocytes that enter meiosis II. Here, the sister chromatids are split apart during anaphase II, resulting in daughter cells called \_\_\_\_\_\_\_\_\_\_\_\_\_, which will undergo cell differentiation to become spermatozoa.

Answer 241

Spermatozoa 3,000 Puberty Spermatogonia (diploid) Primary spermatocytes (diploid) Secondary spermatocytes (haploid) Spermatides

Question 242

The cell differentiation process of spermatides is called \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. The spermatids are remodeled into spermatozoa; this includes the condensation of the nucleus, the rearrangement of organelles, the elongation of the cell and formation of the flagellum. The Golgi will eventually develop into the \_\_\_\_\_\_\_\_; the mitochondria will relocate to base of flagellum; and most of the cytoplasm will be lost, forming the “\_\_\_\_\_\_ body”. This process occurs toward the basal end of the tubule.

Answer 242

Spermiogenesis Acrosome Residual body

Question 243

All spermatogonia are located in the basal compartment; they undergo mitosis in the basal compartment and then become primary spermatocytes here; once the become primary spermatocytes, they begin moving into the ___________ compartment during prophase I of meiosis I. The remainder of spermatogenesis and spermiogenesis occurs in the ____________ compartment

Answer 243

Adlumenal Adlumenal

Question 244

Spermatozoa are released into the ________ of the seminiferous tubules; they remain underdeveloped at this point and will undergo maturation as they move through the male reproductive tract with further maturation occuring once they enter the female reproductive tract. Spermatozoa will enter the ____ \_\_\_\_\_\_\_\_\_\_ and move into the ______ epididymis and through the body and tail epididymides; at the tail epididymis, spermatozoa will remain until _______ \_\_\_\_\_\_\_\_\_\_. Once this occurs, spermatozoa move into the vas deferens, which wraps behind the urinary bladder and ends at the __________ duct; at the ___________ duct, seminial fluid from the seminal vesicles will mix with the sperm prior to ejaculation through the urethra.

Answer 244

Lumen Rete testes Head Sexual stimulation Ejaculatory duct Ejaculatory duct

Question 245

How long do spermatozoa travel through the epididymis?

Answer 245

Movement through the epididymis takes about 12 days, and a great deal of maturation occurs during this time

Question 246

\_\_\_% of seminal fluid is produced by the seminal vesicles

Answer 246

60%

Question 247

The seminal vesciles produce a yellowish, ___________ solution high in \_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_, and prostaglandins. The prostate gland secrets a \_\_\_\_\_\_\_, alkaline fluid. The bulbourethral glands secrete far less than the other glands, and they produce a \_\_\_\_\_\_\_\_, thick mucus that is critical for _________ the urethra for sperm travel.

Answer 247

Alkaline Vitamin C Fructose Milky Clear Lubricating

Question 248

Know this general figure.

Question 249

Testosterone production follows the delta ______ pathway.

Answer 249

Delta 4

Question 250

Question 251

Question 252

Question 253

The gonadotropins LH and FSH regulate testosterone production and spermatogenesis. LH binds its receptor on _______ cell, which express and produce the LHR. The LHR is a GPCR, and once activated, it leads to increased _____ and activation of _____ (i.e., CREB - cyclic AMP response element) ultimately leading to increased expression of steroidogenic genes (e.g., StAR, P450c17, and growth factors) required for converting ________ to _________ to testosterone

Answer 253

Leydig cells cAMP PKA Cholesterol Pregnenolone

Question 254

FSH binds its receptor on ________ cells; the FSHR is a GPCR that once activated increases cAMP levels and PKA activation (i.e., CREB), ultimately leading to increased transcription of genes related to __________ and _________ regulation (e.g., \_\_\_\_\_\_\_, a peptide protein hormone; AMH, growth factors, ________ \_\_\_\_\_\_\_\_\_protein (ABP), and others) The testosterone produced by the Leydig cells can bind the _________ receptor within Sertoli cells, which help regulate the events occurring within the Sertoli cells.

Answer 254

Sertoli cells Spermatogenesis Reproductive regulation Inhibin Adrogen binding protein Androgen receptor

Question 255

GnRH is regulated by \_\_\_\_\_\_\_\_\_-1, a hormone produced by ____ neurons in the _______ nucleus. This hormone is required for activation of the hypothalamic-pituitary-testicular axis. Testosterone negatively feedbacks to the __________ pituitary gland and the ________ nucleus of the hypothalamus, thereby inhibiting the production of \_\_\_\_\_\_\_\_\_\_-1

Answer 255

Kisspeptin-1 KNDy neurons Arcuate nucleus of the hypothalamus Anterior pituitary gland Arcuate nucleus Inhibiting production of kisspeptin-1

Question 256

\_\_\_\_\_\_\_\_\_\_\_ \_, produced by the Sertoli cells, negatively feedbacks to the anterior pituitary gland with its primary effects inhibiting FSH production.

Answer 256

Inhibin B

Question 257

Question 258

In \_\_\_\_\_\_\_\_\_\_\_, testosterone levels rise late in first trimester in association with male sexual differentiation.

Answer 258

Embryogenesis

Question 259

During the neonatal period, testosterone levels rise in the first ___ months of life and decline by age \_\_\_\_\_, remaining low until puberty (due to increased LH, Sertoli, Leydig, and germ cells).

Answer 259

Six 1 year

Question 260

\_\_\_\_\_\_\_\_\_\_\_ is the age at which individuals reach sexual maturity, where they can reproduce

Answer 260

Puberty

Question 261

In males, _______________ occurs around age 6‐7 years and _________ occurs around 11-12 years.

Answer 261

Adrenarche Puberty

Question 262

The onset of puberty is associated with _____________ sleep surges of ________ with secretion later increasing throughout the day. This surge results in maturation of Leydig cells and initiation of spermatogenesis, as well as testicular enlargement, reddening and wrinkling of scrotal skin, pubic hair growth; later increase in penis, prostate, seminal vesicles, and epididymis size; characteristic hair growth, enlarged larynx and thickened vocal cords, enhanced rate of linear growth

Answer 262

Increased LH

Question 263

Increased _____ production results in increased _________ levels; pulses and amplitude of ____ increase at night with secretion increasing throughout the day until maturity is reached

Answer 263

LH Testosterone LH

Question 264

Question 265

Pre-puberty, _______________ completely inhibits GnRH production despite the presence of \_\_\_\_\_\_\_\_\_\_, a strong stimulator of GnRH. In early puberty, _____ neurons increase and produce \_\_\_\_\_\_\_\_\_\_\_\_\_, neurokinin B, and dymorphin, which are believed to have strong stimulatory effects on GnRH, even in presence of GABA.

Answer 265

Gamma aminobutyric acid (GABA) Glutamate KNDy Kisspeptin-1

Question 266

In men, puberty is usually completed by age 16‐18 years. _____ growth is not maximal until mid‐ to late‐20s. As men age, ________ decrease, slowing beard growth, causingregression of reproductive accessory organs and some skeletal muscle, and decreasing male sex drive. By age 40, men see a gradual decrease in free ___________ and an __________ in SHBG. Elderly men have decreased _______ \_\_\_\_\_\_\_\_\_\_ and elevated ___ and \_\_\_\_. Betwen 50 and 80 years of age, sperm production is decreased by 30%. You usually see a decline in sexual activity.

Answer 266

Hair Androgens Free testosterone Increase in sex-hormone binding globulin Total testosterone LH and FSH

Question 267

Question 268

The ______________ layer is the site of implanation.

Answer 268

Endometrial

Question 269

What lines the ovary?

Answer 269

Tunica albuginea

Question 270

What lines the uterus?

Answer 270

Germinal epithelium, simple cuboidal epithelial cells

Question 271

The follicle houses the \_\_\_\_\_\_, which is surrounded by _______ cells

Answer 271

Oocyte Granulosa

Question 272

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ granulosa cells directly surround the oocyte and form the _________ \_\_\_\_\_\_\_\_\_.

Answer 272

Cumulous granulosa cells Corona radiata

Question 273

\_\_\_\_\_\_\_\_\_ granulosa cells do not directly surround the oocyte.

Answer 273

Mural granulosa cells

Question 274

Granulosa cells are important in producing \_\_\_\_\_\_\_\_\_\_\_; they have tight communication with the oocyte facilitated by __________ between granulosa cells and with the oocyte; this communication influences follicle and oocyte development

Answer 274

Estradiol Gap junctions

Question 275

Surrounding the granulosa cells is the __________ membrane; all vascular components are outside of this membrane; therefore all nutrients and gases must diffuse across

Answer 275

Basement

Question 276

As the follicle develops, theca cells develop, ultimately resulting in a theca _____ layer and a theca ________ layer. Theca cells are important in producing ________ but are converted into estradiol by the granulosa cells.

Answer 276

Interna Externa Androgens

Question 277

Question 278

Ovarian steroids are derived from dietary cholesterol, mostly LDL, where it is taken into ovarian cells and stored as cholesterol esters in lipid droplets until stimulation occurs. Ovarian steroidogenesis requires both the granulosa and theca cells in a process called the ______________________________________ meaning that ovarian steroidogenesis requires both two cell types and two gonadotropin hormones. During follicular development, theca cells will express ____ receptors, and granulosa cells will express ____ receptors. When ___ binds to its receptors on theca cells, it promotes steroidogenesis via the Δ5 pathway, ultimately leading to the upregulation of StAR and production of \_\_\_\_\_\_\_\_\_\_\_\_\_, which diffuses across the basement membrane into the granulosa cells. ____ binds its receptors on granulosa cells and upregulates production of \_\_\_\_\_\_\_\_\_\_, the enzyme that converts androstenedione into estradiol, which will enter circulation.

Answer 278

Two-Cell, Two-Gonadotropin Theory LH receptors FSH receptors LH Androstenedione FSH Aromatase

Question 279

Question 280

What is folliculogenesis?

Answer 280

The growth of the follicle from the primordial to ovulatory stage

Question 281

The early stages of follicular development are gonadotropin \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 281

Independent

Question 282

Provide an overview of folliculogenesis.

Answer 282

1. Primordial follicles: the oocyte surrounded by single layer of flattened epithelial cells (precursor granulosa); basement membrane surrounds this layer; in utero 2. Oocyte stimulates primary follicle by secreting local growth factors, promoting differentiation pre-granulosa into granulosa cells; flattened epithelial layer to single layer of cuboidal epithelium, 3. Growth factors from the oocyte continue; additional layer of granulosa cells, secondary follicle. A more well-developed zona pellucida, a layer of glycoprotein-rich extracellular matrix secreted by the oocyte . Stromal cells begin to form theca cells. Movement from primordial to secondary follicular stages can take months (average \>120 days) 4. Granulosa cells continue to proliferate, developing more layers; does not become antral follicle until antrum 5. Graafian follicle develops; very few follicles reach this stage; follicle is ready to receive stimulus and to release. Well developed theca interna, externa; multiple layers of granulosa cells; a well-developed antrum; an oocyte with a surrounding corona radiata connected to the rest of the mural granulosa cells via a stalk; at this stage these granulosa cells have started to express LH receptors, which is key to what occurs next

Question 283

It is only when we reach the __________ follicular stage that the theca and granulosa cells become responsive to gonadotropins

Answer 283

Antral

Question 284

\_\_\_\_\_\_\_\_\_\_\_ refers to ovarian degeneration or death.

Answer 284

Atresia

Question 285

Question 286

Answer 286

* The initial recruitment of ovarian follicles occurs throughout a woman’s life, and before gonadotropin-dependent, they will eventually die by atresia * LH and FSH at puberty allow antral follicles to be recruited and become Graafian follicles, and after puberty, every month, 8 to 10 follicles may be recruited, but typically only one follicle makes it to the Graafian stage and is released; initial recruitment continues throughout a women’s life * The combination of initiation and cyclic recruitment ultimately leads to ovarian follicle depletion, and menopause occurs

Question 287

What is ovulation?

Answer 287

The release of a mature oocyte from a dominant follicle

Question 288

Prior to ovulation, the outer wall of the follicle protrudes from the ovary forming a....?

Answer 288

Stigma

Question 289

What causes rupture of the follicle?

Answer 289

Proteases

Question 290

The oocyte is released into the ____________ cavity along with follicular fluid during \_\_\_\_\_\_\_\_\_\_\_\_.

Answer 290

Perioteneal cavity Ovulation

Question 291

The oocyte remains surrounded by the __________ \_\_\_\_\_\_\_\_\_\_ immediately following ovulation.

Answer 291

Corona radiata

Question 292

The ruptured follicle fills with blood forming the _________ \_\_\_\_\_\_\_\_\_\_\_.

Answer 292

Corpus hemorrhagicum

Question 293

The corpus hemorrhagicum is absorbed and the _________ \_\_\_\_\_\_\_\_ forms.

Answer 293

Corpus luteum

Question 294

What is luteinization?

Answer 294

The process by which granulosa cells differentiate into progesterone-producing cells

Question 295

The corpus luteum degenerates by a process called \_\_\_\_\_\_\_\_\_\_\_\_\_, leaving nothing more than a scar also called a ______ \_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 295

Involution Corpus albicans

Question 296

Question 297

Answer 297

When we look at conversion of steroidogenesis, we go from the Δ5 to Δ4 pathway as we shift from the theca/granulosa cells to the luteal cells

Question 298

The ovarian cycle begins at \_\_\_\_\_\_\_\_\_\_\_. It normally lasts 28 days. It consists of two phases: __________ (1 - 14 days) and ___________ (14 - 28 days).

Answer 298

Puberty Follicular Luteal

Question 299

Which phase of the ovarian cycle involves growth and differentiation of the follicles?

Answer 299

Follicular phase

Question 300

Which phase of the ovarian cycle involves formation and demise of the corpus luteum?

Answer 300

Luteal phase

Question 301

GnRH is produced in hypothalamus, released into the hypophyseal portal system, etc. Higher brain centers moderate the release of GnRH, including \_\_\_\_\_\_\_\_\_\_\_. Initially, LH binds theca cells to produce androstenedione, and FSH binds granulosa cells to stimulate aromatase, which leads to androgen conversion to estradiol. Estradiol _________ feedbacks to the _________ pituitary, slowing LH and FSH production. Once an estradiol threshold is reached, a __________ feedback loop begins, resulting in a surge of LH and FSH. The ___ surge stimulates ovulation and luteinization. If pregnancy does not occur, the resultant _____ \_\_\_\_\_\_\_\_ will degenerate.

Answer 301

Kisspeptin-1 Negatively Anterior pituitary Positive LH surge Corpus luteum

Question 302

Question 303

When estradiol levels reach more than _________ picograms/ml, the ____ surge occurs.

Answer 303

200 pg/ml LH surge

Question 304

Answer 304

Two higher brain centers are involved in GnRH regulation: the arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). The ARC regulates GnRH pulsatility (GnRH must be released in a pulsatile fashion for proper functioning). The AVPV regulates GnRH surge. Together, these nuclei produce kisspeptin-1, which stimulates the release of GnRH, and GnRH stimulates production and release of LH (pulsatile) and FS. Negative feedback on the hypothalamus by estradiol occurs at the ARC while positive feedback occurs at the AVPV – therefore we are able to have both positive and negative feedback in GnRH regulation

Question 305

What nucleus regulates GnRH pulstaility?

Answer 305

Arcuate

Question 306

Which nucleus regulates GnRH surge?

Answer 306

AVPV (anteroventral periventricular nucleus)

Question 307

What does AVPV stand for?

Answer 307

Anterventral periventricular

Question 308

Glycoproteins are also important in regulation. _____________ \_\_ is produced in the developing follicle; inhibin A is produced by the ______ \_\_\_\_\_\_. As follicles are stimulated by FSH, an increase in _________ \_\_\_ expression occurs, which engages in a ______ feedback loop with the anterior pituitary and inhibits FSH synthesis and release

Answer 308

Inhibin B Corpus luteum Inhibin B Negative

Question 309

\_\_\_\_\_\_\_\_\_\_ is a local glycoprotein in the pituitary, and it has same beta subunit as inhibin. It locally _________ FSH synthesis and release.

Answer 309

Activin Stimulates

Question 310

Activin can be inhibited by _________ (also produced in the pituitary), which binds and prevents activin from stimulating FSH production

Answer 310

Follistatin

Question 311

Question 312

Oogenesis begins before birth in utero as germ cells migrate to the bipotential gonads in early development around week 5; as they migrate, oogonium undergo mitosis and proliferate, ultimately forming _________ \_\_\_\_\_\_\_\_\_\_\_ that are then incorporated into _____________ follicles – this also occurs during infancy and childhood, where the ________ \_\_\_\_\_\_\_\_\_ are arrested in ________ I, which can be visualized by the presence of a nuclear envelope around the oocyte. The oocyte remains arrested in ________ I as it moves from a primary to secondary follicle and is not restimulated into meiosis until the ____ surge, which triggers the resumption of meiosis; a key marker of this is the __________ \_\_\_\_\_\_\_\_\_\_ breakdown or nuclear envelope breakdown. After the primary oocyte is stimulated to resume meiosis, it becomes a _____________ oocyte and arrests in __________ II. The _________ oocyte will be released and ovulated from the ___________ follicle; if and only if it is _________ will the __________ oocyte undergo complete meiosis

Answer 312

Primordial oocytes Primordial follicles Primary oocytes Prophase I Prophase I LH surge Germinal vesicle Secondary oocyte Metaphase II Secondary oocyte Graffian follicle Fertilized Secondary oocyte

Question 313

Answer 313

Important notes: 1. Primary oocytes arrests in prophase I 2. Primary oocyte resumes meosis I after LH surge 3. Secondary oocyte arrests in metaphase II 4. Secondary oocyte will not complete meiosis unless fertilization occyrs 5. After meiosis I, we get our first polar body

Question 314

Female duct system includes the _________ (fallopian/uterine tubes), \_\_\_\_\_\_\_, and vagina. Cilia on _________ create currents within peritoneal fluid to carry oocyte into \_\_\_\_\_\_. Oocyte carried towards uterus by combination of _______ and beating of cilia. Fertilization usually occurs within the \_\_\_\_\_\_\_\_\_\_\_. \_\_\_\_\_\_\_\_\_\_cells within oviduct keep oocyte (and sperm if present) moist and nourished

Answer 314

Oviducts Uterus Fimbrae Oviducts Peristalsis Ampulla Mucosa

Question 315

Question 316

The ___________ is the site of sperm reception, and the lower part of the vagina forms the _________ \_\_\_\_\_\_\_.

Answer 316

Vagina Birth canal

Question 317

The __________ is a hollow, pear-shaped, muscular organ (~7cm long) that functions to receive, retain, and nourish a fertilized ovum.

Answer 317

Uterus

Question 318

The wall of the uterus has ____ layers: the ________________ or outermost layer, the ______________ or the bulky, middle layer, and the _____________ endometrium or the mucosal lining of uterine cavity and site of implantation.

Answer 318

Three Perimetrium Myometrium Endometrium

Question 319

Which layer of the uterine wall is composed of interlacing bundles of smooth muscle that contract during childbirth?

Answer 319

Myometrium

Question 320

What is the cervix?

Answer 320

narrow neck of uterus, projecting into vagina

Question 321

What is the purpose of cervical mucus?

Answer 321

·prevents spread of bacteria from vagina into uterus, blocks entry of sperm except at midcycle, lubricates vagina

Question 322

Around day 14, we see the thinning of the cervical mucus, coinciding with increased estradiol production and \_\_\_\_\_\_\_\_\_\_.

Answer 322

Ovulation

Question 323

There are two layers of the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. Stratum ______________ undergoes cyclic changes and is shed during menstruation, and the tratum __________ forms new functionalis after menstruation

Answer 323

Endometrium Stratum functionalis Stratum basalis

Question 324

The uterine artery breaks off into ___________ arteries. The ____________ artery supplies blood to the stratum basalis. The coiled artery supplies blood to the stratum \_\_\_\_\_\_\_\_\_\_\_\_\_. It is the ________ arteries that respond to changes in progesterone and estradiol. When the corpus luteum degrades, the decreased production of progesterone causes the _______ arteries to undergo _________ and death, ultimately leading to menstruation.

Answer 324

Radial Straight Stratum functionalis Coiled or spiral arteries Coiled or spiral arteries Ischemia

Question 325

The endometrial veins are thin walled with ___________ (or swellings)

Answer 325

Sinusoids

Question 326

There are three phases to the uterine or endometrial cycle: \_\_\_\_\_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 326

Menstrual Proliferative Secretory

Question 327

The secretory phase of the __________ cycle can be divided into two subphases: ________ and \_\_\_\_\_\_\_\_\_\_\_.

Answer 327

Uterine Early Late

Question 328

If no fertilization occurs, we see a decrease in the corpus luteum and progesterone and an increase in ________ arteries that kink and spasm, resulting in shedding of the __________ \_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 328

Coiled arteries Stratum functionalis

Question 329

The menstrual cycle is composed of both the _________ and __________ cycles. Estrogen acts in the uterus to induce proliferation of the \_\_\_\_\_\_\_\_\_\_. Estrogen and FSH induce ________ growth and differentiation, resulting in higher estrogen levels. Estrogen reaches a threshold concentration causing a surge of both ___ and ____ to be released from the anterior pituitary. The ___ surge results in ______________ and formation __________ \_\_\_\_\_\_\_\_\_, which produces large amounts of \_\_\_\_\_\_\_\_\_\_\_\_, which stimulates the further build-up of the cells in the endometrium and the uterine glands to secrete substances that maintain the endometrium. High estrogen and progesterone levels strongly ______ LH and FSH release, ultimately leading to the demise of the ___________ \_\_\_\_\_\_\_\_\_\_. These decreased estrogen and progesterone levels also lead to ________ and eventual shedding of endometrium.

Answer 329

Ovarian Uterine Endometrium Follicular LH and FSH LH surge Ovulation Corpus luteum Progesterone Inhibit Corpus luteum Ischemia

Question 330

Take a look.

Question 331

More menstrual cycle stuff.

Question 332

What are some of the extraovarian functions of estrogen?

Answer 332

Maintain normal vasculature, decrease bone resorption, increase blood-clotting factors, increase blood coagulation, increase HDL and triglyceride turnover. Ultimately estrogen has many protective effects for vasculature, bone, and neuron development.

Question 333

What are some extraovarian functions of progesterone?

Answer 333

Contributes to insulin resistance, increases body temperature, and increase minute ventilation

Question 334

Answer 334

Pre-puberty, FSH and LH are synthesized as early as 5 weeks gestation and peak in the pituitary between 25-29 weeks before LH declines Postnatally, serum FSH increases and remains elevated for 2-4 years (decrease likely due to CNS events) By 8-10 years, gonadotropin secretion increases again, with rise in FSH before LH

Question 335

- Adrenarche (7-8 years) - Amplification of a sleep-related pattern of LH release, followed by more permanent increase - Increased estradiol production (& testosterone) - Menarche (first menstruation; 12 years) - Ovulation occurs 6-9 months after menarche - Adolescent growth spurt (skeleton, muscle, viscera) - Increase in hip width and body composition (fat) - Breast development - Growth of axillary and pubic hair (pubarche)

Answer 335

These are all actions that occur during puberty

Question 336

Be familiar.

Question 337

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is the entire period during which estrogen levels decrease due to depletio of ovarian follicles.

Answer 337

Climacteric

Question 338

\_\_\_\_\_\_\_\_\_\_\_ is the time at which the final menstrual bleeding occurs (~52 years)

Answer 338

Menopause

Question 339

Menopause before the age of 35 is considered ___________ \_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_.

Answer 339

Premature ovarian failure

Question 340

Menopause diagnosis is \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, meaning it occurs approximately 6 - 12 months after the last menses and confirmed via increased FSH levels.

Answer 340

Retrospective

Question 341

Why do we see increased FSH levels in menopause?

Answer 341

As estrogen levels decrease due to ovarian reserve depletion, there is no longer estradiol formed to engage in negative feedback with the arcuate nucleus of the hypothalamus

Question 342

What are some early consequences of estrogen depletion (menopause)?

Answer 342

Vasomotor instability (hot flashes), flushing, sweating, increased heart rate, sleep disturbance, fatigue, urogenital atrophy, painful intercourse, thin skin, decreased axillary/pubic hair

Question 343

What are some long-term consequences of estrogen depletion (menopause)?

Answer 343

Loss of bone mass, osteoporotic fractures, increased central obesity

Question 344

Don't forget the positive feedback system for childbirth!

Answer 344