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Physiology > Male Reproductive Phys > Flashcards

Male Reproductive Phys Flashcards

1
Q

Testosterone in Men

A
  • 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
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2
Q

Puberty

A
  • gonadarche- growth of pubic hair, increased testosterone, spermatogenesis & testicular growth
  • precocious puberty= early puberty (before age 9)
  • hypogonadism- impaired hypothal/pit/gonadal axis
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3
Q

Tanner Stages

A

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

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4
Q

Adrenarche

A

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
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5
Q

Functional Hypothal pit axis

A

Pulsatile GnRH is rate limiting

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6
Q

GnRh Pulsemaker

A

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.

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7
Q

LH & FSH stimulate Testes- puberty

A

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

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8
Q

Testicular Hormones

A

androgens= testosterone & DHT

estrogens= estradiol & estrone

peptdies/GFs= Inhibin B/A & activin

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9
Q

2 cell theory

A

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
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10
Q

Androgen Biosynthesis

A

17b- HSD1= androstenedione to testosterone & estrone to estradiol

17b-HSD2= testosterone to androstenedione & estradiol to estrone

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11
Q

Male HPG axis

A

Inhibin regulates FSH release from ant pit

GnRH neurons no steroid R- indirect suppression

Inhibin binds to TGF R in pit.

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12
Q

Hypothal Pit axis 2

A

neruons secreting GnRH via Kisspeptin neurons w/ f steroid R

Testosterone aromatized to estrogen, binds to ER.

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13
Q

Tight Regulation

A

High GnRH, LH & Testosterone peaks directly correlated

Pulsatile GnRH directly reg LH which modulates testosterone secretion from testes.

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14
Q

Sertoli Cell Spermatogenesis Reg

A

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!

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15
Q

Summary

A
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16
Q

Binding Proteins

A

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
17
Q

ABP

A

Regulated by FSH

binds testosterone

intra testicular testosterone storage reservoir

18
Q

Albumin

A

Low binding

Transport from testis to periph tissues

Dissociate readily

19
Q

SHBG

A

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!

20
Q

Bioavailable Testosterone

A

Unbound Testosterone= 1-2%

Bound to albumin= 40-50%

Tightly bound to SHBG= 40-50%

Increase in SHBG reduce amount of bioavailable testosterone

21
Q

Circulating Hormones

A

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)

22
Q

Testosterone Pathway 1

A

Testosterone acts directly on AR in cell

T cross cell mem

T binds directly w/ nuclear androgen R (AR) to regulate gene transcription

23
Q

Testosterone Pathway 2

A

T converted to DHT

T cross cel mme

converted by 5 a reductase

DHT binds with nuclear AR to reg gene transcription

24
Q

T Pathway 3

A

Testosterone converted to estrogen

T cross cell mem

T converted by aromatase into estrogen

Estrogen binds w/ nER to regulate gene transcription

25
Q

T Pathway 4

A

T binds to mem bound AR

Doesnt cross cell mem

stimultes rapid non genomic effects

26
Q

Summary of T pathways

A
27
Q

Testosterone Effects on m. & growth

A
  • stimulate protein syn
  • increase lean body mass
  • decrease fat mass
  • suggests that testosterone may have greates effect on GH in liver to change IGF release.
  • regulates LDL, HDL & VLDL
28
Q

Gynecomastia

A

Benign enlargement of male breast

altered estrogen to androgen balance; high estrogen levels

  • from testes due to hCG
  • peripheral conversion

Physiological: neonates, pubescent boys, elderly

Pathalogical: drug use, high lead in blood, tumors

29
Q

Anabolic Steroid Use

A

prolonged use can atrophy testicles, infertility, no erection but increased libido

30
Q

Aging

A

Gradual decline in testosterone, hypogonadism

Testosterone decrease, increase in SBHG = reduce bioavailable testosterone

Free amt of T also reduced

31
Q

Decreased Testosterone

A

decreased:

E

libido

sex f

m. mass & f

bone mass

32
Q

Aging & Spermatogenesis

A

Testosterone & sperm production highly correletated

Men can father a child at old age but may take longer

33
Q

Hip Fractures

A

Men with low T and low estradiol E2 are at greatest risk of non traumatic hip fractures

34
Q

BHP

A

normal part when prostate gland enlarges in older men due to DHT

Urinary freq

urinary urgency

difficulty urinating

incomplete bladder emptying

straining

dribbling

decrease urine flow

enlarged prostate on PE

35
Q

DHT & prostate cancer

A

DHT stimulates:

  • elevated prostate specific antigen PSA
  • cell growth
  • cell curvival
36
Q

DHT & androgenetic alopecia

A

alopecia & patter alopecia

Typically in men over 40

Elevated 5a reductase levels connection b/t BPH & male pattern baldness

Physiology (11 decks)

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