"Medical Physiology Male Reproductive Endocrinology Brian Howell" 4/6 Flashcards
What is TDF?
Testes determining factor
encoded ny SRY gene on Y chromosome
In what kind of male are normal testes never produced?
XX male, where SRY gene jumped to C chromosome
Infertility
Androgens produced by the Leydig cells promote:
- differentiation of Wolffian ducts - requires testosterone
- Prostate development - requires DHT
Anti-mullerian hormone from Sertoli cells causes mullerian ducts to degenerate
In males, the mesonephros becomes:
the epididymis
The Wolffian duct becomes:
the ductus deferens, seminal vesicles and ejaculatory duct
In females, the mullerian ducts become:
uterine tube, uterus, cervix
Constant levels as opposed to pulsatile, of GnRH, result in:
suppression of LH and FSH
Increase in Leydig cells is dependent on:
Maternal HCG in early development, embryonic LH in late development
What happens at male puberty?
Frequency and amplitude of GnRH pulses increase
Sensitivity of HP axis to testosterone decreases
Gonadotroph sensitivity to GnRH increases
LH and FSH production increase
Spermatogenesis begins
Androgen changes occur (secondary sex characteristics)
Draw out the HP-testicular axis
Hypothalamus makes GnRH
GnRH acts on AP to produce LH and FSH
FSH acts on Sertoli cells to produce inhibin (and growth factors, proteins etc.)
Inhibin negatively feeds back to AP
LH acts on Leydig cells to produce testosterone
Testosterone has a positive paracrine effect on Sertoli cells
Testosterone negatively feeds back to AP and Hypo
What is the effect of FSH on Sertoli cells?
- ABP - keeps T in testes
- P450 aromatase - makes estrogen
- inhibins - feedback, suppress Leydig cell proliferation
- Growth factors for sperm production - ie increase LH receptors on Leydig cells
What is the fx of estradiol in male stuff?
Damps down activity of Leydig cells
What is the function of beta-endorphin?
Beta-endorphin, made by Leydig cells - inhibit Sertoli cell proliferation
What is Kallman syndrome?
Hypogonadotropic hypogonadism No LH or FSH Congenital anosmia Pts fail to enter puberty Mutations in KAL-1X, FGFR1, PROK2, PROKR2, failure of GnRH cells to migrate into the hypothalamus Long-term consequence is osteoporosis
Desmolase, aka P450 side chain cleavage enzyme, does what?
Converts cholesterol to pregnenolone, step up-regulated by LH***
Rxn in mitochondria
How is estradiol made?
Adrostenedione via aromatase –> estrone –> estradiol
Or
Testosterone via aromatase –> estradiol
Happens in Sertoli cells
What enzyme converts T to DHT?
5-alpha-reductase
Rxn mostly occurs in peripheral tissues
What is male pseudohermaphroditism?
- 5-alpha-reductase deficiency (1 cause, but anything that interferes with male androgen synthesis causes MPH)
- Androgen insensitivity syndrome (T and DHT levels okay but no androgen receptors, genitalia develop as women)
What are the symptoms of 5-alpha-reductase deficiency?
DHT levels reduced, T levels okay
Failure of DHT-developement, ie external genitalia or prostate
Why do men have higher HCT levels than women?
Androgens increase the expression of EPO in the kidneys which leads to higher HCT.
How is T bound?
T is bound to albumin and sex-hormone binding golbulin. Only 2% of T is free and that is the active stuff.
What is Kennedy’s Disease (aka Spinobulbar Muscular Atrophy)?
Mutation in androgen receptors causes LMN disease
CAG repeat expansion causes polyglutamine expansion in androgen receptor
Toxic gain of fx
Progressive weakness due to degeneration of LMN in brain stem and spinal cord
Presents similarly to ALS but does not affect the diaphragm.
X-linked
Why does anabolic steroid abuse cause reduced sperm count?
Extra T feeds back to AP and leads to low levels of FSH and LH. Leads to low T in testes (no LH or ABP) which cannot promote sperm development.
What nervous input maintains detumescence?
Sympathetic from T11-L2
Sympathetic also responsible for ejaculation and emission
What nervous input is responsible for tumescence?
PS from S2-S4
Also a little involved in ejaculation
Somatic fibers to the penis travel via:
pudendal nerves to striated muscles of the penis
Also contributes to erection
Why do DM patients have ED?
Vascular disease and autonomic dysfunction mean that input to vascular smooth muscle and endothelium is compromised.
