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PHRM 100 – APPP > APPP 25 and 28: Endocrine System > Flashcards

APPP 25 and 28: Endocrine System Flashcards

1
Q

What is the function of the endocrine system?

A

governs all physiological activities in the human body – includes regulation of (in response to external changes in environment):

  • the different developmental stages
  • metabolism and energy utilization
  • sexual reproduction
  • regulation of homeostasis
  • chemical reactions in cells (therefore controls functions of organs, tissues, and cells)
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2
Q

What structures does the endocrine system include?

A

all organs of the body that secrete signal-transduction molecules (hormones) that travel to the target organs through blood circulation

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3
Q

What is the basic structure of the endocrine system?

A

glands secrete hormones into the bloodstream, which are then transported to target tissues

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4
Q

What is the exocrine system?

A

system of glands producing substances that are excreted via ducts or hollow lumen

  • ie. sweat, salivary, mammary, stomach/GI
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5
Q

What is endocrine signaling?

A

compounds that are produced from a regulatory organ, secreted into, and distributed by the circulation system to multiple distant organs and regulate their functions

  • ie. thyroid and steroid hormones
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6
Q

What is autocrine signaling?

A

compounds that are produced and usually secreted and signal to the same cell

  • ie. interleukin-1 in monocytes is secreted and binds cell surface receptors on those same monocytes
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7
Q

What is paracrine signaling?

A

substances that are produced and secreted near target tissues

  • ie. clotting factors, angiogenic factors, etc.
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8
Q

What are the primary endocrine organs? (4)

A
  • pituitary gland
  • pineal gland
  • thyroid and parathyroid glands
  • adrenal gland – cortex and medulla
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9
Q

What other organs have endocrine cells? (4)

A
  • hypothalamus
  • gonads – ovaries and testes
  • pancreas
  • thymus
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10
Q

What are the 3 mechanisms of hormone release?

A
  • humoral: in response to changing levels of ions or nutrients in the blood (Ca2+)
  • neural: stimulation by nerves
  • hormonal: stimulation received from other hormones
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11
Q

What are hormones?

A

signal transduction molecules secreted from endocrine glands that travel to the target organs through blood circulation

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12
Q

What are the different biochemical forms of hormones? (4)

A
  • peptide (protein) hormones
  • amino acid hormones
  • hormones derived from fatty acids
  • steroid hormones
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13
Q

What are peptide hormones?

A
  • gene products
  • cannot cross cell membrane easily due to their size – instead bind to receptors on surface of cells (GPCRs that activate G-proteins), which in turn activate enzymes inside cells
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14
Q

What are some examples of peptide hormones?

A
  • oxytocin (activates GPCR)
  • anti-diuretic hormone (ADH) – vasopressin (activates GPCR)
  • human growth hormone (activates Jak/STAT)
  • all hormones secreted by the hypothalamus, pituitary glands, digestive tract, and pancreas
  • insulin
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15
Q

What are amino acid hormones?

A
  • not limited by their size – may bind to cell surface receptors, as well as cross cell membrane to activate internal receptors
  • synthesized enzymatically from dietary amino acids (tyrosine, tryptophan, and others)
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16
Q

What are some examples of amino acid hormones?

A
  • thyroid hormones (activates nuclear hormone receptors)
  • melatonin (GPCR)
  • epinephrine/norepinephrine (GPCR)
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17
Q

What are hormones derived from fatty acids?

A
  • lipid molecules derived from membrane arachidonic acids
  • binds to and activates membrane-associated GPCR (various kinds) – essential for immune functions and response to tissue injury
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18
Q

What are some examples of hormones derived from fatty acids?

A

arachidonic-acid-derived hormones:

  • prostaglandins (activates GPCR)
  • leukotrienes (activates GPCR)
  • thromboxanes (activates GPCR)
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19
Q

What are steroid hormones?

A
  • lipid molecules derived from cholesterol
  • high partition coefficient allows easy passage through the cell membrane
  • bind to and activate nuclear hormone receptors – leads to transcription of target genes that carry out essential functions
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20
Q

What are some examples of steroid hormones?

A

(all ligands that bind to and activate
transcription factors)

  • estrogen (estrogen receptor)
  • progesterone (progesterone receptor)
  • testosterone (androgen receptor)
  • cortisol (glucocorticoid receptor)
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21
Q

How do nuclear hormone receptors work?

A
  1. steroid hormone enters cells due to their chemical properties and high partition coefficient
  2. find and bind to soluble hormone receptors (ligand-activated transcription factors found either in cytoplasm and move into nucleus after ligand binding, or are already found in nucleus and waiting for ligand to enter)
  3. receptor changes conformation, allowing the recognition and binding of specific DNA elements (hormone responsive elements) located in up to several 100’s of genes
  4. binding recruits transcriptional co-activator (enhance) or transcription co-repressor (reduce), leading to change in the expression of gene products
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22
Q

What do negative and positive feedback loops do?

A

control hormone levels in response to downstream signals

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23
Q

What happens in a negative-feedback loop?

A

hormone release stops in response to decrease in stimulus – return to homeostasis

example:

  • stimulus (eating) raises blood-glucose levels
  • pancreas releases insulin in response to elevated blood glucose
  • blood glucose decreases as it is used by the body or stored in the liver
  • insulin release stops as blood-glucose levels normalize
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24
Q

What happens in a positive-feedback loop?

A

as long as stimulus is present, action of hormone continues (response provides more stimulus) – not at homeostasis, external stop signal is needed

example:

  • infant nursing at mother’s breast stimulates hypothalamus, which stimulates posterior pituitary
  • oxytocin is released, which stimulates milk production and ejection from mammary glands
  • milk release continues as long as infant continues to nurse
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25
Q

Where is the hypothalamus?

A

below the thalamus and right above the brainstem

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26
Q

Where is the pituitary?

A

at the base of the brain, and rests within a hollowed out area of the sphenoid bone called the sella turcica

  • connected to hypothalamus
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27
Q

What does the pineal body contain?

A

pinealocytes

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28
Q

What are the functions of the pineal body? (4)

A
  • synthesizes melatonin
  • inhibits reproductive function
  • protects against damage by free radical
  • sets circadian rhythms (biological clock)
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29
Q

What are the 2 neuroendrocrine functions of the hypothalamus?

A
  • produce hormones and release through portal vein that regulates the release of anterior pituitary hormones (hypothalamic-pituitary axis)
  • produce hormones (ADH and oxytocin) that are transported to the posterior pituitary for storage and release
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30
Q

What is the structure of the hypothalamic-pituitary axis?

A
  • anterior pituitary lobe contains gland cells that are controlled by specific hypothalamic peptide hormones
  • regulatory patterns in the HPA are formed with both negative and positive feedback loops
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31
Q

What is the function of the hypothalamic-anterior pituitary axis?

A
  • governs multiple neuroendocrine regulatory functions of the hypothalamus
  • ensures that endocrine secretion is matched to the demands of a changing environment
  • nervous system receives information about changes in the internal and external environment from the sense organs (feedback loop)
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32
Q

What is the function of oxytocin?

A

(activates GPCR)

  • females: causes contraction of the uterus and ejection of breast milk
  • males: stimulates contraction of the prostate and vas deferens during sexual arousal
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33
Q

What is the function of antidiuretic hormone (ADH/vasopressin)?

A

(activates GPCR)

  • stimulates kidneys to conserve water
  • vasoconstriction
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34
Q

What is the pituitary gland?

A
  • pea-shaped, 1/2 inch gland
  • divided into anterior lobe (75%) and posterior lobe (25%)
  • posterior lobe consists of axon terminals of hypothalamic neurons – stores but does not produce any hormones
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35
Q

What is hormone release by the anterior pituitary controlled by?

A

hypothalamus

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36
Q

Describe the action and regulation of growth hormones.

A
  • GH release from anterior pituitary is regulated by GHRH (+) and somatostatin (-)
  • GH regulates protein synthesis, particularly in skeletal muscle
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37
Q

What are the direct actions of growth hormones? (2)

A
  • stimulate fat breakdown – switch to fatty acid as energy source
  • glycogen to glucose (gluconeogenesis)
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38
Q

What are the indirect actions of growth hormones? (2)

A
  • through activation of insulin-like growth factors
  • stimulate muscle and bone growth
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39
Q

What do all hypothalamic hormones activate?

A

GPCR

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40
Q

What do all anterior pituitary hormones activate?

A

GPCR

  • except GH
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41
Q

Hypothalamic Hormone

Growth-Hormone-releasing Hormone (GHRH) (+)
Somatostatin (-)

  • anterior pituitary hormone
  • primary target organ and their hormones
  • primary functions at target organ(s)
A
  • growth hormone (GH) binding causes dimerization and JAK-STAT activation
  • liver, bone, muscle, kidney, and others – IGF-1
  • stimulates increase in size of muscles and bones
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42
Q

Hypothalamic Hormone

Thyrotropin-releasing Hormone (TRH) (+)
Somatostatin (-)

  • anterior pituitary hormone
  • primary target organ and their hormones
  • primary functions at target organ(s)
A
  • thyroid-stimulating hormone (TSH)
  • thyroid – thyroxine, triodothyronine
  • stimulates thyroid gland
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43
Q

Hypothalamic Hormone

Corticotropin-releasing Hormone (CRH) (+)

  • anterior pituitary hormone
  • primary target organ and their hormones
  • primary functions at target organ(s)
A
  • adrenocorticotropic hormone (ACTH)
  • adrenal cortex – cortisol
  • stimulates adrenal cortex
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44
Q

Hypothalamic Hormone

Gonadotropin-releasing Hormone (GnRH) (+)

  • anterior pituitary hormone
  • primary target organ and their hormones
  • primary functions at target organ(s)
A
  • follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
  • gonads – estrogen, progesterone, testosterone
  • stimulates sexual development in males and females
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45
Q

Hypothalamic Hormone

Dopamine (-)

  • anterior pituitary hormone
  • primary target organ and their hormones
  • primary functions at target organ(s)
A
  • prolactin
  • breast
  • stimulates milk production
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46
Q

Where is the thyroid gland?

A

near the thyroid cartilage of the larynx

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47
Q

What are the 2 distinct cell types of thyroid follicles?

A
  • follicular cells
  • parafollicular or C cells
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48
Q

What do follicular cells do?

A

produce thyroid hormone – such as thyroxine (T4) and triiodothyronine (T3)

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49
Q

What do parafollicular or C cells do?

A

produce calcitonin – peptide hormone that activates calcitonin receptor (GPCR)

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50
Q

What is the primary hormone secreted by the thyroid glands?

A

thyroxine (T4)

  • triiodothyronine (T3) is made in much lesser made
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51
Q

How is triiodothyronine (T3) made?

A

T3 has much greater biological activity and is mostly produced at the target site through deiodination of T4

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52
Q

What is iodine?

A

an essential material for T3 and T4

  • minimal dietary iodine intake is 150 ug/day in adults
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53
Q

How are both T4 and T3 transported?

A

by binding to thyroid-binding globulins (TBG) and albumin

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54
Q

Thyroid Hormone Signal Transduction

A
  • thyroid hormone receptors (TR) are bound to thyroid hormone response elements (TRE or HRE), as heterodimers with the retinoid X receptor (RXR)
  • in absence of T3/T4, transcription activity is repressed
  • T3/T4 binding to TR promotes conformation changes and turns on transcription
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55
Q

What are the 2 cellular functions of thyroid hormones?

A
  • activating genes that control energy utilization, when bound to nuclear thyroid hormone receptor (T3 or T4)
  • increasing ATP production, when bound to mitochondria T3 receptor (p43)
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56
Q

What is the effect and mechanism of thyroid hormones on the heart?

A
  • chronotropic and inotropic
  • increased number of beta-adrenergic receptors, enhanced responses to circulating catecholamines, increased proportion of alpha-myosin heavy chain (with higher ATPase activity)
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57
Q

What is the effect and mechanism of thyroid hormones on adipose tissue?

A
  • catabolic
  • stimulated lipolysis
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58
Q

What is the effect and mechanism of thyroid hormones on mucsle?

A
  • catabolic
  • increased protein breakdown
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59
Q

What is the effect and mechanism of thyroid hormones on bone?

A
  • developmental
  • promote normal growth and skeletal development
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60
Q

What is the effect and mechanism of thyroid hormones on the nervous system?

A
  • developmental
  • promote normal brain development
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61
Q

What is the effect and mechanism of thyroid hormones on the gut?

A
  • metabolic
  • increased rate of carbohydrate absorption
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62
Q

What is the effect and mechanism of thyroid hormones on lipoprotein?

A
  • metabolic
  • formation of LDL receptors
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63
Q

How is thyroid hormone release regulated?

A
  • TSH (produced by anterior pituitary) is the major regulator of thyroid hormone production
  • binds to specific TSH-R (GPCR) to increase the expression of thyroid hormone biosynthesis enzymes
  • increases hormone synthesis and release
  • T4 exerts negative feedback on TSH release at anterior pituitary
  • serum TSH levels remain the most sensitive index for measurement of thyroid function
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64
Q

What are the relative levels of TSH and T4 in hyperthyroidism?

A
  • low TSH
  • high T4
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65
Q

What are the relative levels of TSH and T4 in primary hypothyroidism?

A
  • high TSH
  • low T4
66
Q

What are the relative levels of TSH and T4 in secondary hypothyroidism?

A
  • low TSH
  • low T4
67
Q

What is thyroid dysfunction?

A

most common endocrine dysfunction following diabetes in humans

  • 10x higher in females
68
Q

What is goiter?

A

swollen thyroid glands

  • can occur in both hyperthyroidism and hypothyroidism
69
Q

What is Hashimoto disease?

A

autoimmune disease that leads to hypothyroidism

70
Q

What are the clinical features of hypothyroidism?

A
  • goiter
  • slow heartbeat
  • dry skin
  • cold intolerance
  • weight gain
71
Q

What are the clinical features of hyperthyroidism?

A
  • bulging eyes
  • unblinking stare
  • goiter
  • rapid heartbeat
  • increased sweating
  • heat intolerance
  • unexplained weight loss
72
Q

How many parathyroid glands are there and where are they located?

A
  • 4 glands
  • embedded in posterior of thyroid gland
73
Q

What are the cells of the parathyroid glands?

A
  • oxyphil cells: unknown function
  • chief cells
74
Q

What do chief cells do?

A

produce parathyroid hormone (PTH, 84 aa peptide) in response to lower-than-normal Ca2+ concentrations to restore Ca2+ levels

75
Q

What receptor does parathyroid hormone (PTH) activate?

A

parathyroid hormone receptor (GPCR)

76
Q

What are the primary positive regulators of extracellular Ca2+ levels in healthy adults?

A
  • parathyroid hormone (peptide)
  • calcitrol (dihydroxy-vitamin D3) – produced in kidney, activates nuclear hormone receptor
77
Q

Homeostatic Regulation of Extracellular Ca2+ Ion Concentrations

What happens when the concentration of Ca2+ in blood is too high?

A

thyroid produces calcitonin, which decreases blood Ca2+ by:

  • increasing excretion of Ca2+ by kidneys
  • increasing Ca2+ deposition in bones
  • stopping osteoclasts
78
Q

Homeostatic Regulation of Extracellular Ca2+ Ion Concentrations

What happens when the concentration of Ca2+ in blood is too low?

A

parathyroid glands produce PTH, which increases blood Ca2+ by:

  • releasing stored Ca2+ from bones
  • stimulating production of calcitrol in the kidney, which increases absorption of Ca2+ by the digestive system
  • enhancing reabsorption of Ca2+ by the kidneys
79
Q

Where are the adrenal glands?

A

superior to each kidney

80
Q

Describe the structure of the adrenal glands.

A
  • pyramidal
  • consists of outer cortex and inner medulla layer
81
Q

Adrenal Glands

What is the adrenal medulla?

A
  • part of the sympathetic nervous system
  • secretes norepinephrine and epinephrine
82
Q

Adrenal Glands

What are the 3 regions of the adrenal cortex and what do they secrete?

A

(from outermost layer to innermost layer)

  • zona glomerulosa – secretes mineralocorticoids (salt)
  • zona fasciculata – secretes glucocorticoids (sugar)
  • zona reticularis – secretes adrenal androgens (sex)
83
Q

Describe the process of steroidogenesis.

A
  • cholesterols are taken up from LDL in circulation by LDL receptors on adrenocortical cells
  • in a series of biotransformation reactions mediated by CYP-P450 enzymes, cholesterols are converted to steroid hormones in the mitochondria and smooth endoplasmic reticulum (sER)
  • adrenal cortex produces over 30 steroid hormones (together known as corticosteroids) that are divided into 3 classes based on their function – each class produced by one of the different regions (zona)
84
Q

Steroidogenesis

What corticosteroid does the zona glomerulosa produce?

A

aldosterone

85
Q

Steroidogenesis

What corticosteroid does the zona fasciculata produce?

86
Q

Steroidogenesis

What corticosteroid does the zona reticularis produce?

A

DHEA, DHEAS

87
Q

Hormones of the adrenal cortex are derivatives of what?

A

cholesterol

88
Q

Zona Glomerulosa

A
  • mineralocorticoids
  • control of salt reabsorption
89
Q

Zona Glomerulosa

Describe mineralocorticoid actions.

A
  • at the molecular level, aldosterone enters the kidney’s principle (P) cells and binds to the mineralocorticoid receptor (MR)
  • MR activation increases expression of many responsive genes – epithelial Na+ channel (ENaC – slower effect), and serum and glucocorticoid-regulated kinase 1 (SGK-1) that promotes ENaC activity (fast effect)
  • both cortisol and aldosterone can bind to MR – in mineralocorticoid target tissues, expression of 11βHSD2 (11β-Hydroxysteroid dehydrogenase 2) converts cortisol into inactive metabolite to ensure the MR endocrine signaling is restricted to aldosterone
90
Q

Zona Glomerulosa

What tissues express the mineralocorticoid receptor (MR)? (5)

A
  • kidney
  • sweat glands
  • colon (GI)
  • heart (CVS)
  • hippocampus (CNS)
91
Q

Zona Glomerulosa

What is the renin-angiotensin-aldosterone system (RAAS)?

A

hormone system that regulates blood pressure and fluid and electrolyte balance

92
Q

Zona Glomerulosa

How does the renin-angiotensin-aldosterone system (RAAS) work?

A
  • when renal blood flow is reduced, juxtaglomerular cells in the kidney convert the precursor prorenin (already present in blood) into renin and secrete it directly into circulation
  • plasma renin then carries out the conversion of angiotensinogen (released by the liver) to angiotensin I
  • angiotensin I is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE) found on the surface of vascular endothelial cells, predominantly those of the lungs
93
Q

Zona Glomerulosa

What is the direct effect of angiotensin II?

A

vasoconstriction – results in increased blood pressure

94
Q

Zona Glomerulosa

What hormone does angiotensin II secrete from the adrenal cortex?

A

aldosterone

  • causes renal tubules to increase reabsorption of Na+, which causes reabsorption of water into blood, volume of extracellular fluid in body, which also increases blood pressure
95
Q

Zona Fasciculata

A
  • glucocorticoids
  • stress response
96
Q

Zona Fasciculata

How are glucocorticoid receptors activated?

A
  1. transcriptional activation of target genes
  • at the molecular level, glucocorticoids exert their classical effects through ligand-activated transcription regulation of protein expression
  • unliganded (no hormone) receptor is sequestered by heat shock proteins (HSP) in cytoplasm
  • hormone binding causes change in conformation and translocation to nucleus
  • binding of hormone-GR to DNA glucocorticoids response elements (GRE) in promoter of target genes will induce their transcription
  1. activation of MAPK for fast effects by liganded GR
97
Q

Zona Fasciculata

What are the main actions of glucocorticoids? (3)

A
  • regulate all aspects of metabolisms, stress response
  • mediate organogenesis in different stages of development
  • potent immunosuppressive activity
98
Q

Zona Fasciculata

What are the anti-inflammatory actions of glucocorticoids? (3)

A

through genomic actions:

  • inhibit activation and proliferation of key immune cells (T-lymphocytes and B-lymphocytes, dendritic cells, macrophages, eosinophils, and mast cells)
  • inhibit expression of inflammatory cytokines in immune cells as well as in target tissues
  • inhibit production of antibodies (including both auto- and neutralizing antibodies)
99
Q

Zona Fasciculata

What might the use of glucocorticoids mask?

A

can mask microbial infections – leads to serious, even fatal, delay in treatments

100
Q

Zona Fasciculata

How is glucocorticoid release regulated?

A
  • trauma via nociceptive pathways, afferent from NTS, emotion via limbic system, and circadian rhythm affect CRH
  • HPA corticotropin-releasing hormone (CRH) from hypothalamus regulates release of adrenocorticotropic hormone (ACTH)
  • homeostasis levels of ACTH release follows circadian rhythm in irregular bursts, with highest concentration in early mornings
  • increased ACTH secretion occurs in response to stress and injury
  • glucocorticoids exert a negative feedback on ACTH secretion, both at pituitary and hypothalamus
  • prolonged treatments with anti-inflammatory glucocorticoids may lead to adrenal atrophy and loss of endogenous glucocorticoid output – gradual cessation is necessary
100
Q

Zona Fasciculata

Describe the actions of corticosteroids in the chronic stress response.

A
  • HPA axis is a key regulatory pathway in maintenance of physiological homeostatic processes
  • end product of this pathway (cortisol) is secreted in a pulsatile pattern, with changes in pulse amplitude creating a circadian pattern, with cues from light-dark cycles
  • during acute stress, both epinephrine and cortisol levels rise – acute elevations in these factors are beneficial to promoting survival of the fittest as part of the fight or flight response
  • in chronic stress, cortisol levels remain raised – long-term cortisol exposure becomes maladaptive, which can lead to a broad range of problems including metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease, and increased susceptibility to infections
101
Q

Zona Fasciculata

What happens to cortisol levels during acute stress?

A

both epinephrine and cortisol levels rise

  • acute elevations in these factors are beneficial to promoting survival of the fittest as part of the fight or flight response
102
Q

Zona Fasciculata

What happens to cortisol levels during chronic stress?

A

cortisol levels remain raised

  • long-term cortisol exposure becomes maladaptive, which can lead to a broad range of problems including metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease, and increased susceptibility to infections
103
Q

Zona Reticularis

What controls the secretion of adrenal androgens?

104
Q

Zona Reticularis

What is dehydroepiandrosterone (DHEA)?

A
  • the major form of adrenal androgens
  • is converted into androstenedione (A)
105
Q

Zona Reticularis

What is androstenedione (A)?

A
  • a form of adrenal androgens, produced in a small amount
  • precursor for testosterone and estradiol in peripheral tissue (ie. adipose tissue)
106
Q

Zona Reticularis

What are the actions of the adrenal androgens? (3)

A
  • pre-puberty sexual developments in male and females
  • contribute to small anabolic and sexual developmental effects, but is the major source of estrogen in men
  • provide the major source of estrogen in post-menopausal women
107
Q

What are the ovaries?

A

production of germ cells (ova) and hormones

108
Q

What are uterine (fallopian) tubes?

A

narrow tubes that are attached to the upper part of the uterus and serve as tunnels for ova to travel from ovaries to uterus

109
Q

What is the uterus?

A

womb – able to expand in size to hold a developing baby

110
Q

What is the cervix?

A

lower part of uterus, opening into vagina

111
Q

What is the vagina?

A

birth canal – joins uterus to outside of body

112
Q

What is the menstrual cycle?

A

regular cyclic pattern of the development of female germ cells into ova

113
Q

What are the phases of the menstrual cycle? (3)

A
  • follicular phase
  • ovulation
  • luteal phase
114
Q

What is the follicular phase of the menstrual cycle?

A
  • selection and maturation of a dominant follicle
  • continued production of sex hormone (E2) by two cell types (granulosa and theca) within the follicle
115
Q

What is the ovulation phase of the menstrual cycle?

A

occurs mid-way (d14) in the cycle following the LH surge

116
Q

What is the luteal phase of the menstrual cycle?

A
  • corpus luteum continues the production of sex hormones (P4 and E2) in anticipated support for fertilization
  • continue production of P4 and E2 suppresses LH and FSH release
117
Q

Describe the process of the ovarian synthesis of estradiol.

A

two-cell, two-gonadotropin principle of ovarian steroid hormone production

  • LH controls theca cell production of androstenedione, which diffuses into the adjacent granulosa cells and acts as precursor for estradiol biosynthesis
  • granulosa-cell capacity to convert androstenedione to estradiol is controlled by FSH

(theca cell: cholesterol to progesterone to androstenedione)
(granulosa cell: androstenedione to estrone to estradiol)

118
Q

What are the 3 layers of the uterine wall?

A
  • outer perimetrium
  • middle and muscular myometrium (thickest layer)
  • innermost endometrium (uterine lining) – the only layer that undergoes changes during menstrual cycle
119
Q

Describe the hormonal and endometrial changes during the menstrual cycle.

A
  1. menstrual cycle begins with gradual increase in FSH, promoting follicle development
  • increasing follicular estradiol (F2) secretion inhibits LH and FSH production
  1. at E2 secretion peak, LH surge (and increased FSH, to a lesser extent) causes decrease in E2 and starts production of progesterone (P4)
  • LH surge also results in ovulation

3, following ovulation, corpus luteum took over production of E2 and P4, which inhibits FSH and LH

  1. uterine lining (endometrium) corresponding go through proliferative (growth) phase during follicular development (follicular phase)
  • P4 release with formation of corpus luteum (luteal phase) will induce endometrial differential and gland secretion to prepare for fertilization
  1. in absence of fertilization, corpus luteum regression leads to reduced E2 and P4 levels
  • shedding of endometrium occurs (menstruation)
  1. fall of E2 and P4 levels releases negative feedback on FSH/LH production
  • cycle repeats
120
Q

Molecular Mechanisms of Estrogen Actions

What are the 3 endogenous estrogens?

A
  • estradiol
  • estrone
  • estriol
121
Q

Molecular Mechanisms of Estrogen Actions

A

binding to the classical ER-alpha or ER-beta in the nucleus results in conformational changes, which recruits coactivator or corespressor, which alters gene transcription

122
Q

Molecular Mechanisms of Estrogen Actions

What does the non-genomic pathway of estrogen functions include?

A

direct activation of multiple kinase pathways, including PKA, PKC, and MAPK

123
Q

Estrogen Tissue Effects

What is the effect in the uterus?

A

endometrium proliferation

124
Q

Estrogen Tissue Effects

What is the effect in the ovary?

A

mitotic effects on granulosa cells

125
Q

Estrogen Tissue Effects

What is the effect in the breast?

A

ductal epithelium growth and differentiation

126
Q

Estrogen Tissue Effects

What is the effect in the liver?

A

metabolic modulation

127
Q

Estrogen Tissue Effects

What is the effect in the CNS?

A

neuroprotective

128
Q

Estrogen Tissue Effects

What is the effect in the bone?

A

antiresorptive

129
Q

Estrogen Tissue Effects

What is the effect in the CVS?

A

cardioprotective

130
Q

What are the 5 effects of progesterone?

A
  • anti-estrogenic effects in uterus
  • pro-estrogenic effects in breast
  • pro-thyroid effects
  • anti-inflammatory effects
  • metabolic effects
131
Q

What are the anti-estrogenic effects of progesterone in the uterus? (3)

A
  • decreased uterine motility
  • development of secretory endometrium
  • thickened cervical mucous
132
Q

What is the pro-estrogenic effect of progesterone in the breast?

A

breast growth

133
Q

What are the pro-thyroid effects of progesterone? (2)

A
  • increased body temperature
  • increased appetite
134
Q

What is the anti-inflammatory effect of progesterone?

A

depressed T-cell function

135
Q

What is the metabolic effect of progesterone?

A

anti-insulin – switch to use fat for energy

136
Q

What are the 3 functions of the male reproductive system?

A
  • produce, protect, and transport gametes (sperm) and protective fluid (semen)
  • discharge sperm within female reproductive tract during sex
  • produce and secrete male sex hormones responsible for coordinating these cellular processes
137
Q

What are the 2 endocrine functions of the male reproductive system?

A
  • testosterone is the major male sex hormone in circulation – inside target cells, it can be converted to dihydrotestosterone (DHT), which binds to androgen receptor with higher affinity
  • due to its anabolic (growth) effects, synthetic androgens were widely abused by athletes and body-builders
138
Q

What are the testicles (testes)?

A

oval-shape organs responsible for making testosterone and for generating sperm

139
Q

What is the scrotum?

A

house testes at lower-than-body temperature for sperm production

140
Q

What are the epididymis, vas deferens, and ejaculatory ducts?

A

ductal system for maturation of sperm and feeding to the urethra

141
Q

What is the seminal vesicle?

A

production of semen (ejaculate)

142
Q

What is the prostate gland?

A

contributes additional fluid to semen

143
Q

What are the bulbourethral glands (Cowper’s glands)?

A

produce a clear, slippery fluid that lubricates urethra and maintains neutral pH

144
Q

Structural Components of the Testes

What are seminiferous tubules?

A

coiled masses of tubes within the testes

145
Q

Structural Components of the Testes

What are spermatozoa?

A

immature sperm

  • produced in seminiferous tubules
  • transit through testis and efferent ducts to the epididymis in which they are stored and mature before ejaculation
146
Q

Structural Components of the Testes

What are the main cells?

A
  • Leydig cells
  • Sertoli cells
147
Q

Structural Components of the Testes

What does the interstitial space surrounding the seminiferous tubules contain?

A

testosterone-producing Leydig cells, fibroblasts, and macrophages

148
Q

Structural Components of the Testes

What do seminiferous tubules, bounded by a basal membrane (basal lamina) contain?

A

somatic Sertoli cells and developing germ cells (sperms)

149
Q

Synthesis and Metabolism of Testosterone

Where is the circulating testosterone in males produced?

A
  • majority produced in the testis’ Leydig cells
  • small amount produced from adrenal cortex (zona reticularis)
150
Q

Synthesis and Metabolism of Testosterone

What is testosterone converted into?

A
  • within target cells, converted by enzyme 5-alpha-reductase into dihydrotestosterone (DHT) – which has higher affinity to androgen receptor
  • small amounts are converted to estrogen through action of aromatase (CYP19)
151
Q

Synthesis and Metabolism of Testosterone

How is testosterone metabolized and excreted?

A

metabolized in liver to inactive forms, and excreted through kidney

152
Q

Mechanism of Testosterone Action

A
  • hormone binding results in conformational changes of the androgen receptor and relocation to nucleus
  • in nucleus, hormone-bound receptor interacts with androgen response element of target genes
  • recruitment of co-activators results in altered gene expression
153
Q

What are the actions of androgen in males?

A
  • gonadotropin regulation
  • spermatogenesis
  • sexual differentiation – Wolffian stimulation
  • external virilization – larynx growth and voice deepening, increase in linear bone growth, increase in lean muscle mass, stimulates male-pattern hair growth, increase in skin thickness and sebaceous gland activity
  • stimulates erythropoietin production in kidneys
  • sexual maturation– structural development of reproductive organs, increase in libido, alters mood and behavioural effects
154
Q

Androgen Feedback Regulation

A
  1. LH stimulates Leydig cell secretion of testosterone, while FSH stimulates Serotoli cells for sperm production
  2. testosterone exerts androgenic effects on target tissue, including Serotoli cells
  3. negative feedback loop: testosterone inhibits LH secretion through direct action on pituitary, as well as inhibits secretion of GnRH from hypothalamus
  4. separate negative feedback loop exists between FSH and Serotoli cells secreting inhibin B (TGF-β-like hormone)
155
Q

What are anabolic steroids?

A
  • drug of abuse by athletes and body builders
  • 17-a-alkylated androgens and derivatives
  • used intermittently in high doses to increase lean body mass, enhance performance, sustain intensive trainings, and to improve bulk
156
Q

What are the adverse effects of anabolic steroids? (5)

A
  • decrease spermatogenesis and testicular atrophy
  • gynecomastia
  • liver and kidney damage
  • cardiac hypertrophy, decreases HDL, increases LDL
  • psychological changes
157
Q

Endocrine/Exocrine Secretions in other Organs

Heart

A

specialized muscle cells produce natriuretic peptides in response to high blood pressure

158
Q

Endocrine/Exocrine Secretions in other Organs

Intestine

A

produces hormones important to the coordination of digestive activities

159
Q

Endocrine/Exocrine Secretions in other Organs

Adipose Tissues

A

release leptin as feedback control for appetite

PHRM 100 – APPP (23 decks)

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