Male Reproductive Phys Flashcards
Testosterone in Men
- 7th gestation week, testosterond diff fetal genitourinary tract
- Causes masculiniztion of genitilia by 8 weeks
- Rise again in 3-12 months of life
- Reappeasrs at puberty- spermatogenesis
- After puberty- increases m. mass, sustains spermatogenesis & drives male libido
- Decline after 30
Puberty
- gonadarche- growth of pubic hair, increased testosterone, spermatogenesis & testicular growth
- precocious puberty= early puberty (before age 9)
- hypogonadism- impaired hypothal/pit/gonadal axis
Tanner Stages
Stage 1= adrenarche; prepubertal
stage 2= gonadarche; hair growth 12.3 yr
stage 3= penile growth & gynecomastia 13.9 yr
stage 4= peak body growth 14.7 yr
stage 5= adult genitalia; facial hair 15.3 yr
Adrenarche
Zona reticularis of adrenal begins to secrete DHEA & DHEAS
7-9 in boys; 6-8 girls
no known role
- maturation of adrenal galnd & pulsatile release gonadotropic hormones= indep process!
- adrenal androgens suppress hypothal (GnRH) until gonads reach maturity
- Adrenal androgens likely contribute to axillary hair growth
- patients w/ Addison’s or premature adrenarche= normal
Functional Hypothal pit axis
Pulsatile GnRH is rate limiting
GnRh Pulsemaker
Initiation of puberty depends on GnRH release
GnRH pulse freq determines rate & LH from pituitary
Synchroinzed pulse maker regulates regulates reproductive function!
GnRH correlates w/ LH secretion directly.
LH & FSH stimulate Testes- puberty
once GnRH pulse maker active= multiple endocrine factors work w/ genetics & neurons to regulate release of GnRH, LH, FSH, testosterone
- feedback: testosterone, estrogen, inhibin
+ feedback: no known; but in women induction of ovulation
Testicular Hormones
androgens= testosterone & DHT
estrogens= estradiol & estrone
peptdies/GFs= Inhibin B/A & activin
2 cell theory
Cholestrol- readily available
StAR protein= rate limiting
- StAR shuttles cholesterol from outer to inner mitoch mem, where CYP11A (part of 450 cytochorme rxn) metabolizes it to pregnenolone.
- Pregnenolone shuttled to ER where it is further metabolized
- LH & FSH regulate gonadal steroidogenesis.
- LH binds to LH R on Leydig cell to stim C19 androgen production (testosterone).
- Testosterone diffues into circulation to act in endocrine manner or diffuse across BTB & enter Sertoli cell.
- In Sertoli Cells, testosterone binds w/ AR (nuclear R) to regulate cell f & spermatogenesis
- Some of tesosterone in Sertoli cell doesn’t bind to AR & metabolized by 5ARD into DHT
- DHT binds to AR on Sertoli or secreted into tubular fluids.
- DHT in low levels affect semen & inhibit sperm motility
- FSH binds to R on Sertoli cell to stimulate Inhibin B production (- feedback to FSH in pit)
- FSH also needed for sperm maturation
Androgen Biosynthesis
17b- HSD1= androstenedione to testosterone & estrone to estradiol
17b-HSD2= testosterone to androstenedione & estradiol to estrone
Male HPG axis
Inhibin regulates FSH release from ant pit
GnRH neurons no steroid R- indirect suppression
Inhibin binds to TGF R in pit.
Hypothal Pit axis 2
neruons secreting GnRH via Kisspeptin neurons w/ f steroid R
Testosterone aromatized to estrogen, binds to ER.
Tight Regulation
High GnRH, LH & Testosterone peaks directly correlated
Pulsatile GnRH directly reg LH which modulates testosterone secretion from testes.
Sertoli Cell Spermatogenesis Reg
Spermatogenesis
- testosterone from Leydig
- LH binding to R to stimulate its production
- PRL & Inhibin B act w/ LH to reg testosterone production
- FSH acting on FSH R on Sertoli
- ABP which keeps intracell levels of testosterone high in Sertoli
- Vit A w/ R on Sertoli
DHT in Sertoli cell to exert autocrine effect on f!
***FSH DOESN’T REG DHT!
Summary
Binding Proteins
Androgen Binding Protein= ABP
SHBG
Albumin
- ABP & SHBG from same gene & same aa but ABP found only in Sertoli
- SHBG found in liver & more
- SHBG & Albumin are plasma proteins that bind testosterone:
- SHBG binds testosterone highest affinity
- Albumin lowest affinity
ABP
Regulated by FSH
binds testosterone
intra testicular testosterone storage reservoir
Albumin
Low binding
Transport from testis to periph tissues
Dissociate readily
SHBG
High affinity
DHT>Testosterone> androstenedione> estradiol> estrone
Androgen metabolites recircularted or excreted in urine as conjugated!
Metabolize in liver, Conjugate w/ bile or w/ substances to be excreted in urine.
Majority of SHBG manufactures & released by the liver!
Bioavailable Testosterone
Unbound Testosterone= 1-2%
Bound to albumin= 40-50%
Tightly bound to SHBG= 40-50%
Increase in SHBG reduce amount of bioavailable testosterone
Circulating Hormones
Not the same as bioavailable testosterone.
Circulating measure free T, albumin bound & SHBG bound.
50% in men & women (but in women very little estrogen bound to SHBG)
Testosterone Pathway 1
Testosterone acts directly on AR in cell
T cross cell mem
T binds directly w/ nuclear androgen R (AR) to regulate gene transcription
Testosterone Pathway 2
T converted to DHT
T cross cel mme
converted by 5 a reductase
DHT binds with nuclear AR to reg gene transcription
T Pathway 3
Testosterone converted to estrogen
T cross cell mem
T converted by aromatase into estrogen
Estrogen binds w/ nER to regulate gene transcription
