Reproduction 2 Flashcards
Explain the primary regulatory mechanisms of the HPG axis.
Describe the main pituitary hormones and their effects.
Major hypothalamic hormone:
Gonadotropin-releasing hormone (GnRH/LHRH)
Absolutely required
Must be released in a pulsatile manner
Major pituitary hormones = Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH). LH: stimulates steroidogenesis in ovaries and testes. FSH: stimulates gametogenesis (egg and sperm maturation) in ovaries and testes.
Slide 5
Describe Kisspeptin in regards to the regulation of GnRH?
What is its receptor? Would would mutation in this receptor cause?
Kisspeptin – required to initiate increased GnRH release at the time of puberty. Presumed signal for pubertal onset.
Mutations in KISS1 receptor cause hypogonadotropic hypogonadism
What effect will androgens/estrogens (gonadal steroid hormones) have on GnRH?
Gonadal steroid hormones (androgens/estrogens) – exert negative and positive feedback on GnRH
Describe how the following will affect GnRH:
GnIH prolactin neutrotransmitters (GABA) cortisol (stress) growth factors (TGF alpha/beta) neuropeptides (opiods, melatonin)
almost all inhibit GnRH
What does Inhibin B do? Where is it expressed? Describe how it works.
INHIBIN B – specific inhibitor for FSH
Expressed in gonads
Inhibits FSH beta subunit synthesis in gonadotropes
Slide 7
Where is activin expressed?
What does it do? Where does it act?
ACTIVIN –
Expressed in pituitary and gonads
Stimulates FSH beta, LH beta, and GnRH receptor synthesis in pituitary
Slide 7
Describe the major physiological actions and regulation of the pituitary gonadotropin hormones, LH and FSH, in male reproduction.
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Describe:
PITUITARY GONADOTROPINS “TROPIC HORMONES”
Describe their structure and what they have in common.
Large glycoproteins
Share a common alpha subunit
Beta subunits specify hormone: LH, FSH, TSH
What do LH and FSH do in men and women?
IN GENERAL FOR BOTH SEXES:
LH – stimulates steroidogenesis
FSH – stimulates gametogenesis
In regards to male production, what will FSH stimulate?
What do they act on?
Sertoli cells – have high affinity FSH receptors
Form the blood-testes barrier
FSH –
Stimulates spermatogenesis
Increases sperm motility
Stimulates growth of seminiferous tubules – primary determinant of testes size
Stimulates androgen binding protein (ABP) – maintains high local T
Stimulates aromatase
Stimulates inhibin
Stimulates growth factors
Slide 10
What effect will LH have in male reproduction processes. What will LH stimulate (what cells have LH receptors?)
Leydig cells – have high affinity LH receptors
LH –
Stimulates steroidogenesis from cholesterol
Androgens = 19 carbon steroids
Stimulates StAR protein – rate limiting
Stimulates Leydig cell growth
Describe the type of horomone: androgens
19 carbon steroids
Distinguish between direct actions of testosterone and the actions mediated by DHT and E2 and identify the roles of aromatase and 5α-reductase in steroid metabolism.
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Where are testosterone precursors made?
Testosterone precursors made in extragonadal tissues: brain, adrenal, skin, adipose tissue
What is the primary source for circulating T?
How does T travel in circulation?
What happens to it intracellularly?
Metabolized?
Testes – primary source of circulating T
Circulation – bound to SHBG
Intracellular – converted to estrogens or DHT
Metabolized – diols, triols
What type of receptor do T and DHT bind? Which has a higher affinity for it?
T and DHT both bind androgen receptor (AR)
Nuclear steroid receptor
DHT higher affinity than T for AR
Describe the excretion of testosterone.
How much is excreted as free testosterone?
What happens to T that is not excreted?
less than 2% of daily production is excreted as free testosterone
Remainder is converted to 17-ketosteroids & DHT
conjugated to water soluble forms and excreted.
What does masculinization of the brain require?
Masculinization of the brain requires T to E conversion