Final Exam (after midterm) Flashcards
1
Q
The adrenal gland is…
A
Paired
8-10g
Above, medial, & back to the kidneys
2
Q
Components of adrenal gland
A
Surrounded by fibrous capsule
Divided into functional layers: capsule, adrenal cortex (90%), & adrenal medulla (10-15%)
3
Q
Cortex of adrenal gland
A
Is ~90% of adrenal mass Has 3 zones: - zona glomerusa - zona fasciculata (thickest; ~80%) - zona reticularis
4
Q
Hormones of adrenal gland
A
Aldosterone: synthesized in zona glomerulosa
Cortisol, corticosterone: synthesized in zona fasciculata
Sex steroids: synthesized in zona reticularis
Catecholamines (epinephrine & norepinephrine): synthesized in medulla
5
Q
Initiation of steroidogenesis
A
Formation of pregnenolone from cholesterol (occurs in mitochondria): this is the beginning of all hormones of adrenal gland
- Regulated by steroid acute regulatory (StAR) protein
- A cAMP-inducible gene that increases in response to tropic hormones - P450scc (side-chain cleavase) cleaves side chain of cholesterol to produce pregnenolone (on inner mitochondrial membrane)
6
Q
Synthesis of steroid hormones
A
- All are derived from cholesterol (mostly LDL)
- HDL can be synthesized from acetyl-CoA - Zone specific expression of enzymes determines steroid production
- Enzymes in mitochondria or ER (Steroid intermediates shuttle back & forth) - Most steroids differ by minor modification of side groups (often hydroxyl groups): lead to enormous differences
7
Q
Function of zona fasciculata
A
Produce cortisol
- no storage
- half-life is 70-120 mins
- converted to inactive cortisone & other metabolites by liver & other target cells (can be reconverted)
8
Q
Secretion of cortisol
A
- Cortisol production activated by ACTH
- Begins G-protein/cAMP signaling pathway - Stimulates formation of pregnenolone from cholesterol
- ACTH secretion is pulsatile (circadian rhythm): highest in morning)
- Rapid inc/dec. in response to ACTH pulse (can change due to stress)
* if synthesis of ACTH is suppressed for long time, a months may be needed to resume (this could be due to exogenous administration of cortisol)
9
Q
Transport of circulating cortisol
A
Use: corticosteroid-binding globulin
- Synthesized by liver
- has high affinity for cortisol
- Binds ~ 75% of all cortisol (10% is free, 15% is bound to serum albumin)
- bound cortisol is protected from liver inactivating it (due to delay of metabolic clearance)
10
Q
Cortisol inactivation by liver…
A
Is due to inc. H2O solubility (HSD11B2 (90% of this is secreted by kidneys))
*HSD11B1 can reactivate cortisol
11
Q
Significance of converting cortisol to cortisone
A
Changes depends on need of cortisol and aldosterone
Cortisol can bind to mineralocorticod receptor (MR)
- High conc. can lead to aldosterone-like symptoms (hypertension, hypokalemia, low renin, low aldosterone levels)
Cortisol conc. is 100-1000x higher than aldosterone conc.
- Aldosterone responsive cells need to inactivate cortisol to respond specifically to aldosterone
* Enzyme deficiency of HSD11B2 inc. cortisol; leading to apparent mineralocorticoid excess (AME) syndrome
12
Q
Cortisol receptor
A
Glucocorticoid receptor (NR3C1)
- Functions of cortisol depend on GR
- GR-beta inhibits GR-alpha
- Uses ligand binding to translocate GR into nucleus
- GR response element (GRE) is located on promoters of target genes (binds GR)
13
Q
Metabolic effects of cortisol
A
Inc. transcription of specific genes
Effects: opposite of insulin, similar to GH
- at expense of protein & fat
Action depends on target cells
- muscle cells, adipocytes, & lymphocytes = inc. catabolism
- liver cells = glycogen synthesis
Overall effects: anabolic effect on liver
- inc of blood glucose
14
Q
Anti-inflammatory effects of cortisol
A
Inhibits immune response
Dec. number of lymphocytes & antibody production
Become susceptible to infections
Ex. hydrocortisone cream
Uses 3 mechanisms:
1. Activated inhibitor (IkB) of immune response transcription factor NFkB
- Coactivator w/ C-fos/C-jun
2. GR-cortisol binds & inhibits nuclear migration of NFkB
3. GR competes w/ NFkB for other interacting transcription factors
15
Q
Other effects of cortisol
A
- Hypertension: sensitizes arterioles to action of norepinephrine
- Glycogneolysis -> hyperglycemia: Inc. effect of norepinephrine on carbohydrate metabolism
- Euphoria: inc. activity of CNS
- Inc of extracellular fluid: act as mineralocorticoid b/c it interacts with MR
16
Q
Function of zona glomerulosa
A
Recovery of Na+ in kidney & enhanced K+ secretion into urine (balances charge difference)
Adjustment of ECF
17
Q
Sodium appetite
A
Triggered by negative sodium balance
Not strongly manifested in normal conditions (suppressed)
18
Q
Renin-angiotensin-aldosterone system (secretion of aldosterone)
A
- renin from kidneys converts angiotensinogen (from liver) to angiotensin I (found in lungs)
- Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II (in lungs)
- Comes from endothelial cells of lungs - Angiotensin II stimulates aldosterone secretion (in adrenal cortex) or angiotensin III (degradation product)
19
Q
Renin-angiotensin-aldosterone system (kidney)
A
Macula densa cells: line distal tubule & detect Na+ levels in kidney tubule
Juxtaglomerular cells: line afferent arterioles & detect blood pressure
Pericytes: near afferent arterioles; produce renin based on macula densa & juxtaglomerular cell detections
20
Q
The juxtaglomerular apparatus
A
Consists of pericytes
Source of renin
Found in kidneys
21
Q
Effects of angiotensin II
A
Change in peripheral resistance: rapid pressure response (water retention (higher blood pressure)
Change in renal function: slow pressure response (inc. Na+ absorption/K+ excretion)
Structural changes remodeling: vascular and cardiac hypertrophy & remodeling (stimulates water reabsorption into kidneys)
22
Q
Function of aldosterone
A
Regulate fluid volume
Water absorption
Sodium/potassium homeostasis
- Na+ transport in: distal tubules of kidney, colon, salivary & sweat glands
23
Q
Effects of aldosterone
A
Lag period of response: 1 hr Distal tubules & collecting ducts of kidney
Promotes retention of Na+ and excretion of K+ & H+
Sensitizes arterioles to vasoconstrictor agents
Rise in plasma volume & blood pressure
24
Q
Natriuretic peptides (general)
A
Two main types: ANP & BNP Produced in the heart muscle cells & stored in granules Receptors are present in glomeruli, medullary collecting ducts of kidney, zona glomerulosa of adrenal cortex, & peripheral arterioles Function: - Dec. renin production - Inc. excretion of H2O & Na+ - Inc. glomerular filtration - Reduces blood volume/pressure
25
Production of sex steroids
Mainly synthesized in gonads
- Synthesis is regulated by gonadotrophins
Adrenal cortex contributes to production of DHEA & androstenedione
- Regulated by ACTH & hypothalamic CRH
Converted to testosterone in peripheral tissues
26
Adrenal medulla (general)
Total mass = 1g
15% of adrenal gland weight
Creates fight/flight response by inc. blood pressure & cardiac output and dilating pupils
27
What are the adrenal medulla & chromaffin cells part of?
Sympathetic nervous system
| *Chromaffin cells are modified neurons
28
Adrenal medulla releases catecholamines via...
Pre-ganglionic neurons releasing acetylcholine to stimulate adrenal medulla
Steps:
1. Tyrosine is translated into dopa via tyrosine hydroxylase (rate limiting step)
2. Dopa is translated into dopamine via dopa decarboxylase
3. Dopamine is translated into norepinephrine via dopamine beta-hydroxylase
4. Norepinephrine is translated into epinephrine via Phenylethanolamine N-methyltransferase (PNMT)
*PNMT is stimulated from cortisol
*stored in granules
29
Hormones of the adrenal medulla
Catecholamines (20% norepinephrine & 80% epinephrine)
Met-enkephalin & leu-enkephalin
- co-secreted with catecholamines
- Can block neurotransmitters (endogenous analgesics)
Released due to stimuli
30
Fight or flight response
From adrenal medulla nervous system
Major hormones: catecholamines
Occurs at expense of other organs
Epinephrine: rapidly mobilizes fatty acids as primary fuel for muscles
Norepinephrine: elicits responses for cardiovascular system (inc. blood flow; dec. insulin secretion)
Also uses ACTH to release about 30 other hormones
31
Acute fight/flight response is...
Integrated adjustment of many complex processes in organs vital to response
32
Adrenergic receptors (general)
alpha & beta 1 bind to epinephrine (E) & norepinephrine (NE)
beta 2 binds to epinephrine mostly
Different target tissues = different responses
- Drugs specific to receptors have different effects
33
Alpha 1 adrenergic receptor
Target: smooth muscle
Potency: NE>/=E
Action: Gq
34
Alpha 2 adrenergic receptor
Target: nerve terminals
Potency: E>NE
Action: Gi
35
Beta 1 adrenergic receptor
Target: heart, cerebral cortex
Potency: NE>E
Action: Gs
36
Beta 2 adrenergic receptor
Target: lung, smooth muscle, cerebellum
Potency: E>NE
Action: Gs
37
Cardiac stimulation leading to greater cardiac output: which is greater (E or NE)?
Epinephrine >> norepinephrine
38
Constriction of blood vessels; leading to inc. peripheral resistance; to inc. arterial pressure: which is greater (E or NE)?
Norepinephrine > epinephrine
39
Increasing metabolism: which is greater (E or NE)?
Epinephrine >> norepinephrine
40
Disorders of the adrenomedullary
```
Adrenomedullary deficiency
Epinephrine deficiency
Hypotension
Hypoglycemia
Adrenal catecholamines
Pheochromocytoma
```
41
Cells of the exocrine pancreas
Acinar cells: secretion of digestive enzymes (proteases, amylase, lipase)
Duct cells: secretion of NaHCO3
Secrete into duodenum
42
Cells of endocrine pancreas
alpha-cells: glucagon
beta-cells: insulin
delta-cells: somatostatin
epsilon-cell: ghrelin
F-cells: pancreatic polypeptide
All hormones that are secreted into blood (veing capillaries)
*glucagon, somatostatin, pancreatic polypeptide, & ghrelin also produced by cells of the gastrointestinal mucosa
43
What are the islets of Langerhans also called?
The endocrine pancreas
2% of total mass
Consists of 3 mill. islets
44
The blood supply of the pancreas
Aortic artery: hepatic artery branching
| Portal vein: splenic and mesenteric veins
45
The islets of Langerhans are...
highly vascularized
Blood supplies beta-cells first -> alpha- & delta-cells
Heterogenous (variable)
46
Beta-cells of islets
Function together
Proliferation is minimal after 5 years
Avg lifespan = 25 years
Immature beta-cells are called neogenic niches (surround the beta-cell islets)
Alpha- & delta-cells transdifferentiate under extreme beta-cell loss
47
Insulin granules
Each is made by 51 a.a.
Metabolized in the liver (C-peptide (part of proinsulin) is metabolized in kidney)
beta-cells contain 5,000-8,000 granules
Half-life: 5 days
Young granules = deeper in cytoplasm; more mobile (faster)
Older granules: degrade intracellularly
Each contain insulin hexamer stabilized by calcium & zinc
48
Steps of insulin release from beta-cells
Glucose is main stimulator
- hexokinase is glucose sensors
1. Glucose is taken into beta cells by GLUT2
2. Aerobic glycolysis + inc. of ATP/ADP ratio
3. Inhibition of ATP-sensitive K+ channels (reduce K+ efflux)
4. Voltage-gated Ca2+ channels open
5. Inc. Ca2+ triggers exocytosis of insulin-containing granules
6. Ca2+ activated potassium channels opens; leads to repolarization of membrane
7. Metabolic coupling factors are generated during glucose metabolism; facilitate exocytosis and/or proinsulin synthesis
8. GLP-1/related peptides bind GLP-1 receptors & trigger cAMP production. Amplifies pathway, ion channels, & exocytosis (allows insulin to leave cells)
49
Regulation of insulin secretion
Vagus nerve: acts as sensory neuron & motor neuron (main neuronal coordinator of appetite control, digestion, & metabolism)
- Release of acetylcholine in pancreas stimulates insulin release
50
Homeostasis of glucose
Regulated by hormones that affect appetite & cell metabolism
51
Hormones effecting blood glucose levels
```
Major:
- Insulin (only hormone that lowers blood glucose)
- Glucagon (inc. blood glucose)
Minor:
- Epinephrine
- Cortisol
- Growth hormone
- Thyroid hormone
- Secretin
- Cholecystokinin
Act together to form integrated control system
```
52
Regulation of blood glucose
Serum glucose during fasting: 3-5mM (normal is below 6.1)
- Glucose from liver is tightly regulated at this time
Serum glucose after meal: 7mM (bad is above 11)
Insulin: synthesizes protein, lipid, & glycogen and inhibits their degradation (use glucose)
- Targets: liver, muscle, adipose tissue
Glucagon inc. catabolic processes (mostly in liver) & fatty acid mobilization
53
Liver vs muscle glucose metabolism
Liver:
- Has glucagon receptor
- Produces F26BP
- Pyruvate kinase is phosphorylated by PKA
54
how insulin promotes glucose uptake/organ
Insulin promotes glucose uptake in muscle & adipose tissue
- Inc. GLUT4 transporters on cell surface
Insulin promotes glucose uptake in liver
- stimulates glucokinase & promotes phosphorylation of glucose to form glucose 6-phosphate
55
Steps of fuel metabolism during prolonged fasting
1. Protein degradation yields glucogenic amino acids
2. Urea is exported to kidney & excreted in urine
3. Citric acid cycle intermediate is diverted to gluconeogenesis
4. Glucose is exported via bloodstream to brain
5. Fatty acids are oxidized as fuel (producing acetyl-CoA)
6. Lack of oxaloacetate prevents acetyl-CoA entry into citric acid cycle (acetyl-CoA accumulates)
7. Acetyl-Coa accumulation favors ketone body synthesis
8. Ketone bodies are exported via bloodstream to brain for fuel
9. Excess ketone bodies go to urine
56
Hormonal regulation of food intake
alpha-MSH & NPY neurons receive hormonal input from peripheral organs
- alpha-MSH neurons regulate neurons that stimulate anorexia & catabolism (less eating)
- NPY neurons stimulate orexia & anabolism (more eating)
57
Type 1 diabetes mellitus
```
5-10% of cases
Insufficient production of insulin
Mostly due to autoimmune destruction of beta-cells
Usually develops early in life
Idiopathic
```
58
Type 2 diabetes mellitus
```
80-95% of cases
Insulin resistance
Usually develops in late adulthood
Associated with obesity
Cells don't respond correctly to insulin
```
59
Insulin resistance is due to:
```
Pre-receptor
- antibodies against insulin
- mutant insulin
Receptor
- reduced INSR expression
- reduced affinity for insulin
- impaired tyrosine-kinase activity
- INSR antibodies
```
60
Symptoms of diabetes
```
Blood sugar elevated
- Body tries to dilute glucose; leads to excess urination/thirst
Type 1: high production of ketone bodies
- Fat breakdown is accelerated
Type 1: dramatic weight loss
```
61
What are the long-term effects of elevated blood sugar?
Proteins are glycosylated
Excessive glucose causes glycation
Hemoglobin is glycated b/c entry of glucose into erythrocytes is not regulated
- compromises O2 delivery
- impaired injury repair
Inc. risk of cardiovascular disease, renal failure, & small blood vessels & nerve damage
62
Symptoms of prolonged type 2 diabetes
```
Abdominal obesity
High triglycerides
Low HDL
High blood pressure
Elevated blood glucose
```
63
The pathway from obesity to type 2 diabetes
Called the "lipid burden" hypothesis
1. Adipocytes become packed
- Can't accomodate TAG
2. No TAG deposit leads to FA in blood
3. Excess FA enters muscle & liver
- Create TAG lipid droplets
- Cause these organs to lose sensitivity to insulin (interferes with GLUT4 movement)
4. Blood glucose levels rise
64
Ways to treat diabetes
Weight loss
- reduces insulin resistance, hepatic glucose production, & fasting hyperinsulinemia
- less calorie intake = adipose tissue-derived NEFA provides fuel for muscle, liver, & myocardium
Metformin & Thiazolidinediones
- inc. insulin sensitivity
- dec. glucose output by liver
Sulfonylureas & Meglitinides
- promote insulin secretion from pancreas
GLP-1 receptor agonists
- inc. insulin secretion
Alpha-glucosidase inhibitors
- dec. the absorption of carbohydrates from intestine
65
Wolffian ducts
Male
Epididymis & vas deferens
Occurs if antimullerian hormone exists (regresses Mullerian duct)
66
Mullerian ducts
Female
Uterus & oviduct
Occurs if NR2F2 (orphan nuclear receptor) exists (regresses Wolffian duct by stopping FGF)
67
Steps of sexual differentiation
1. Establishment of genetic sex
2. Translation of genetic sex to gonadal sex
3. Translation of gonadal sex to phenotypic sex
68
Human sex chromosome
Either X or Y chromosome (number 23)
69
X chromosome statistics
About 160 megabases (Mb) long
Represents 5% of genome
Encodes about 850 proteins
- Regulate gametogenesis & hypothalamus-pituitary functions
- Most regulate non-reproductive functions
70
Y chromosome statistics
About 60 Mb long
Represents 2% of genome
Encode about 57 proteins
- Most regulate reproductive functions
71
Sex chromosome aneuploidy is...
Nondisjunction of sister chromatids during meiosis
72
Sex chromosome mosaicism is...
Nondisjunction of sister chromatids in zygote
73
What did Alfred Jost determine about sexual differentiation?
Testes are needed for male sexual differentiation
| Ovaries are not necessary for female differentiation (are not hormone dependent)
74
What is needed for normal sex differentiation?
- Normal intact chromosome complement
- Fully functioning sex determination genes
- Intact steroidogenic pathway and receptors
75
XX male occurs...
When SRY gene is on an X chromosome
76
XY female occurs...
When there is a deleted or mutated SRY gene on a Y chromosome
77
Purpose of SRY gene
Only on Y chromosome
| Binds to DNA to induce transcription of other genes
78
Germ cell development to gonadal cells
1. Primordial germ cells differentiate in allantoic ectoderm
2. Migrate to endoderm & along hindgut to genital ridges
3. Are polar during migration
- Migration involves cell protrusion & adhesion in leading edge/retraction in lagging edge
4. Guiding cells biochemically direct the migration
79
Defects in testosterone synthesis or actions cause...
```
Phenotypic female (XY)
No ovaries
Undescended testes
Infertility
Blind ending vagina
```
80
Defects in testosterone synthesis or actions are caused by...
Translation doesn't occur at any stage between cholesterol and androgen synthesis
81
Congenital adrenal hyperplasia (CAH) causes...
Hyperplasia of adrenal glands before birth ->
Excessive androgen production ->
Masculinization of genitalia
82
Congenital adrenal hyperplasia is caused by...
Addition of testosterone during development
| - Causes DHT (an androgen)
83
Sexual differentiation of the brain is...
A marked difference between the sexes in the structure and behaviour of the brain
*Occurs during a critial time period (different for each species)
84
Sexual differentiation of the hypothalamus (male)
Testosterone freely enters brain & converts to estradiol
| Has tonic center: controls LH/FSH post-puberty
85
Sexual differentiation of the hypothalamus (female)
Estradiol produced by fetal ovary can't cross blood-brain barrier
Retains surge center + tonic center: control LH/FSH after puberty
86
Puberty includes...
All physiological, morphological, & behavioral changes that occur in the growing animal as gonads/brain/phenotype change from adolescent to adult
Begins:
- Female: frist cycle
- Male: first ejaculation
87
Control of puberty
By pulsatility of GnRH release (regulated from neural mechanism in hypothalamus)
- LH and FSH present in pituitary and hypothalamus before puberty, but not released
* Pulsatile administration of GnRH induced menstrual cycle in prepubertal monkeys
88
What are the endocrine mechanisms of puberty?
Levels of GnRH rise (in amplitude & frequency)
- Caused by dec. sensitivity of tonic center to negative feedback from gonadal steroids
Surge center (females only) does not change sensitivity
- Before puberty, E2 levels aren't high enough to stimulate surge release
- After puberty, has E2 has positive feedback on surge center & release of GnRH
Result in pulses of LH/FSH increasing and levels of steroids increasing
- Inhibin is able to stop FSH secretion if E2 levels are too high
89
Regulation of GnRH
Kisspeptin (KISS1) neurons are located in anteroventral periventricular & arcuate nuclei of the hypothalamus
- Express estrogen and androgen receptors
- Signal through its receptor (KISS1R) in GnRH neurons to regulate pulsatile secretion of GnRH
There are two types of KISS1 neurons
- They respond differently to steroid feedback
90
GnRH (general)
Small peptide (10aa) cleaved from larger precursor
Released with gonadotrophin associated peptide (GAP)
Synthesized by 1-3K neurons in hypothalamus
- Axons terminate in either hypophyseal portal capillaries to release GnRH or other brain areas to affect sexual behavior
GnRH is also synthesized in placenta, gonads, breasts, lymphocytes, & pituitary (the function of these is unknown)
91
Actions of LH and FSH
Similar to ACTH
Inc. intracellular cholesterol
Transport cholesterol to inner mitochondrial membrane (using StAR)
- Rate limiting step
Convert pregnenolone by side-chain cleavage
Target cells: male & female reproductive
- Testis: LH acts on Leydig cells (testosterone)& FSH on Sertoli cells (estradiol)
- Ovaries: Both LH & FSH are steroidogenic; act on theca interna (testosterone) & granulosa cells (estradiol). LH also acts on luteal cells (progesterone)
92
During spermatogenesis there are three different important cell types. These are?
Spermatogonia: cells that become sperm (main)
Sertoli cells: physically support differentiation process
Leydig cells: produce testosterone
93
Androgen synthesis & secretion (males)
Most important androgens secreted by testes: DHEA, testosterone (over 95%)
- 4-10mg/day
- 98% is bounds to albumin & sex-hormone-binding globulin
Testosterone: acts on internal genitalia development & muscle cells
Testosterone (not DHT) can be converted to estradiol
94
Action of androgens (males)
Powerful anabolic hormone
In young children: occasional pulses (nocturnal) of LH & FSH -> production of steroid hormones -> high enough level to produce secondary sex characteristics
95
Oocyte of female
Mitosis of oogonia occurs before 1st meiotic division
Millions of oocytes remain in prophase I until ovulated
Primordial follicles: single cell layer surrounding oocyte
96
Loss of oocytes
Highest number of oocytes (~7mill) at 5th month in womb
At birth: ~1.5mill oocytes
Progressive loss of oocytes after birth
About 400-500 ovulations occur in lifetime
97
Formation of corpus luteum
Called luteinization
Tonic center produces GnRH
CL maintains basal levels of LH
LH stimulates the CL to secrete P4
98
Hormones of estrous cycle
Progesterone (P4): highest during luteal phase; declines during follicular phase
Estradiol (E2): peaks during middle of luteal & middle of follicular phase
FSH: Peaks at beginning & end of luteal phase and end of follicular phase
LH: Peaks at end of follicular phase
99
Steps of conception & implantation
Fertilization of ovum occurs in oviduct
1. Hydrolytic enzymes in acrosome of sperm loosen expanded cumulus cells & zona pellucida around ovum
2. One sperm penetrates & fertilizes oocyte
3. Causes cortical reaction & exocytosis of Ca outside plasma membrane
- Zona becomes impermeable to other sperm
4. Ciliated cells move the zygote along the oviduct to uterus
5. Zygote begins to divide & derives energy from oviductal & uterine secretions until implantation
100
What are the changes that occur in the uterine endometrium during the menstrual cycle?
Days 1-3: breakdown
Days 3-14: estrogenic proliferative phase
Days 14-28: Progestational secretory phase
101
Ways to prevent conception (female)
Intrauterine device: molded plastic devices that disrupt normal uterine environment (sperm can't get to oocytes)
Tubal ligation: tying the tubes
Oral (every day) & transdermal (3 patches): stop P4 & E2 synthesis
Injection (once a month) & implant (once a month): stops P4 synthesis
102
Ways to prevent conception (male)
Very little ideas on hormonal contraceptives
Condoms
Vasectomy: tying the tubes
103
Types of anti-progesterones
RU486: receptor complex binds but genes do not activate
ONA: receptor complex does not bind
104
Secretion of placental hormones
Human chorionic gonadotropin (hCG) is secreted by placenta
- Maintains the CL
- Serves as an indicator of pregnancy
Progesterone (P4) production is taken over by placenta at around 2.5 months into pregnancy
105
What are the changes in the breast during pregnancy?
Normal estrogen levels: stimulate duct formation & accumulation of fat
- Inc. during pregnancy
Glucocorticoids, prolactin, & placental lactogen: induce enzymes for milk production
- During nursing, prolactin levels stay high: inhibit normal cycling of GnRH (prevent ovulation)
Estrogen & progesterone: high concentrations prevent milk production
- After parturition, E2 & P4 levels fall: milk production begins
106
How to reduce symptoms associated with menopause:
Symptoms: vasomotor, osteoporosis, short-term memory change, depression...
Hormonal replacement therapy (HRT): estrogen or estrogen + progesterone
- Almost 75% of women don't need HRT
107
What happens to GH in adults?
Deficiency
Symptoms:
- Cardiovascular risk
- Reduced bone health
108
What happens to thyroid hormone in adults?
```
Hypothyroidism
Presents multiple clinical symptoms:
- Myxedema
- Coma
Treatment: L-T4 replacement
```
109
Statistics of menopause
At age 51: affects ~90% of women
At age 37.5: oocyte pool is reduced to ~25K
- Increased rate of follicular atresia after this
110
Advantages & disadvantages of HRT
Estrogen can inc. risk of endometrial & breast cancer
- Progesterone promotes conversion of estradiol to estrone. Estrone has low affinity to estrogen receptors so can reduce cancer risk
- Long-term effects of progesterone are unknown
Without treatment: bone loss = 1-2% each year (inc. risk of bone fractures)
Estrogen is used to decrease depression due to menopause
111
Prevalence of doping
High school, college, & professional athletes ~ 11%
| Hollywood actors above 40 years = 50%
112
How caffeine is considered doping
```
A methylxanthine (purine metabolites)
Exerts effects by:
- Inc. cAMP by inhibition of phosphodiesterase
- Translocation of Ca for inc. neuro-muscular availability
Sport beneficial causes:
- Enhanced nervous function
- Inc. cardiovascular function
Banned in large doses for sports
Most beneficial: in endurance events
Legal limit: 15ug/ml (6-8 cups coffee)
```
113
How beta blockers are considered doping
```
Uses:
- Reduce blood pressure
- For migraine headaches
- Reduces heart arrhythmia
- For alcohol withdrawal & anxiety
Function:
- Block beta receptor in cardiac muscles (reduce anxiety, jitters, & slows heart rate
Most beneficial: in sports needing steady hands
```
114
How erythropoietin (EPO) is considered doping
```
Uses:
- Stimulates RBC production
- Inc. hematocrit
- Inc. oxygen carrying capacity
Most beneficial: in heavy working sports
```
115
What do steroidogenic enzymes depend on?
```
Electron transfer proteins
Mitochondrial electron transporters:
- ADR
- ADX
Microsomal electron transporters:
- POR
- B5
```
116
What is the function of CYP21A2?
Drives production of aldosterone & cortisol of steroidogenesis
117
Inactivation of catecholamines
Done via COMT or MAO
| - Develop pathways to VMA, which is excreted
118
What occurs when there is high blood glucose?
Dec. glucogen breakdown
Inc. glucogen synthesis
Inc. glycolysis
119
Ways to diagnosis diabetes:
Check blood glucose levels
- Normal: 6.1mmol/L; 110mg/dl
Check hemoglobin
- Normal: Less than 5.7%
120
What is the normal peak concentration of testosterone during male development?
10nmol/L
121
Two types of cells surround a follicle; they are:
Theca interna cells: CYP17A1 (capable of synthesizing own androgens)
- Uses LH
Granulosa cells: CYP19A1 (need androgens from theca cells)
- Uses FSH
122
Causes of ovulation
- Elevated blood flow
- Breakdown of connective tissue
- Ovarian contractions
All lead to rupture of follicular wall
123
What are phytoestrogens?
```
Outside sources (food)
Are not steroids
- Are able to interact with steroid hormones
```
124
Function of phytoestrogens on hormones
```
Inhibit TPO
- Result in hypothyroidism
Inc. SHBG (sex hormone)
- Inc half-life of sex steroids
Can bind to estrogen receptors
Induce IGF-1
- Positive effect on bone physiology
Inhibit GnRH
Inc. insulin sensitivity
Induce Adiponectin
Inhibit PSA
* Positive & negative effects
```
