Male Reproductive Endocrinology Flashcards
what causes genotypic sex, gonadal sex and phenotypic sex?
genotypic: y chromosome
gonadal: SRY gene encodes TDF- testis transcription factor
phenotypic: hormones produced by gonads
what is the phenotypic sex?
development of accessory sex organs, external genitalia and secondary sex characteristics
what does SRY cause?
development of gonad and germ cells into testes and spermatogonia
what hormone causes the development of external genitalia?
dihydrotestosterone (DHT)
what causes XX males? what is the impact on gonads?
the SRY gene translocates to the x chromosome in crossing over
normal testis are not produced but it is still male
describe the surroundings of the indifferent gonad
it is associated with the mesonephros, the excretory (wolffian) duct and the paramesonephric (mullerian) ducts
what do the mesonephros, wolffian duct and mullerian ducts form in the male fetus?
mesonephros- epididymis
wolffian- vas deferens, seminal vesicles and ejaculatory duct
mullerian ducts degenerate
what to the mullerian ducts form in the female? what prevents this in the male?
fallopian tubes, uterus and cervix
anti mullerian hormon from sertoli cells causes degeneration
what do androgens produced by the leydig cells promote? which androgen is required for each?
differentiation of the wolffian duct (requires testosterone) and prostate development (requires DHT)
in the absence of testosterone, what happens to the external genetalia?
female structures are formed (homologies between male and female)
what does the hypothalamic-pituitary-testis axis regulate in males? what is the feedback mechanism?
spermatogenesis and androgen production
testis products inhibi hypothalamus and anterior pituitary
describe the release of GnRH, LH and FSH in males? what happens with constant GnRH release?
pulsatile
constant levels of GnRH prevent LH and FSH release by downregulating receptors
what is another name for kallmann syndrome? what mutations cause it?
hypogonadotropic hypogonadism
KAL-1, FGFR1, PROK2 and PROKR1
what are the two main consequences of hypogonadotropic hypogonadism?
anosmia (inability to smell) and lack LH and FSH
link between the developmental origin of olfactory cells and GnRH producing cells
what is the main danger for patients with kallmann syndrome?
osteoperosis- hormone replacement therapy indicated
what causes the proliferation of leydig cells in the prenatal stage of male development?
maternal chorionic gonadotropin (early development) and embryonic leutinizing hormone (late development)
describe the activity of the hypothalamic-pituitary-gonadal axis prior to puberty
few GnRH pulses with low LH and FSH levels
high negative feedback sensitivity
spermatogonia are diploid and undifferentiated in the testis
what 6 events happen in male puberty?
GnRH pulses increase (frequency and amplitude), negative feedback decrease, gonadotroph sensitivity to GnRH increases, LH and FSH production increase, testosterone increase (with spermatogenesis) and androgen changes of puberty occur
where are the receptors for LH? what does stimulation do?
Leydig cells- transcribe proteins involved in testosterone biosynthesis
where does FSH bind and what are the results?
binds to the basolateral membrane of sertoli cells stimulating transcription and synthesis of aromatase, growth factors, ABP and inhibin
what are the two negative feedback routs of the hypothalamic-pituitary-testicular axis?
1) testosterone inhibits GnRH release and LH release
2) inhibin inhibits FSH release
what is the effect of LH binding on Leydig cells?
GPCR produces cAMP and activates PKA
increases enzymes in testosterone synthesis, stimulates rate limiting step and stimulates sterol carrior protein and activating protein
what are the 4 primary actions of FSH?
on sertoli cells
increases androgen binding protein (keeps local testosterone high), P450 aromatase (produces estrogen), growth factors to support sperm productiion and inhibins that supress leydig cell proliferation and FSH secretion
what are the secondary effects of FSH?
acts on Leydig cells and increases sperm motility
how do Leydig cells and Sertoli cells act upon eachother?
L cells make testosterone- acts on S cells
S cells convert T into estradiol (aromatase)- acts on L cells
S cells generate growth factors that act on L cells
what is the precursor for androgen synthesis? where does the first step occur?
cholesterol
mitochondria
what is the rate limiting step of androgen synthesis and what stimulates it?
desmolase producing pregnenolone
up regulated by LH
what are the extratesticular sources of androgens?
adipose tissue, skin and adrenal glands
what causes male pseudohermaphroditism?
any deficit in the mechanism by which androgens act in genetic males
what is the result of 5 alpha reductase deficiency?
DHT levels are reduced and testosterone levels are normal- faialure of urogenital sinus and external genitalia development
what does androgen insensitivity syndrome cause? how?
male pseudohermaphroditism
androgen receptors are defective- UG sinus and external genitalia are female and wolffian ducts degenerate
what are the two types of androgen effects in the body?
androgenic: maturation of the sex organs and development of secondary sex characteristics
anabolic: promote protein synthesis, muscle growth and increase bone strength and length
what causes maturation of bones indirectly in men? what is the result on bone growth?
estradiol metabolites- more gradual in men than women
how do men and women’s brains compare?
men have a larger brain but women have more dendritic connections
how do gonadotropins compare in males and females? what causes the difference?
male FSH levels are 8 times higher because of E2 (estrogen), testosterone and DHT
why do men have a higher hematocrit than women?
because androgens increase expression of erythropoietin from the kidneys
what type of receptor binds androgens and which androgen has highest affinity?
homodimeric receptor to direct transcription
DHT has greater activity than testosterone
what portion of testosterone is biologically active and what percentage of total testosterone is it?
free in the blood- only 2%
what is another name for andropause and what is the consequence?
senescence- not an abrupt loss of fertility but decrease in testosterone and quantity and quality of sperm. gonadotropins increase (mid 50s)
when are there spikes and general increases in testosterone?
during fetal development, short lived increase after birth and low levels until puberty
what are the effects of reduced testosterone?
decreased bone formation, muscle mass, appetite, libido and hematocrit
what patients should be treated with testosterone therapy?
those with low testosterone below 300ng/dL and without prostate or breast cancer
what does finasteride do and how? what are the side effects?
blocks DHT production to treat male pattern baldness
side effects: impotence, abnormal ejaculation and depression
what can be a result of too much testosterone?
cause prostatic hyertrophy or cancer, causes congestive heart failure and high RBC count
what are effects of anabolic steroid abuse?
reduced sperm count, testicle shrinkage, permanent heart, liver and kidney damage, psychiactric problems, breast enlargement in men and excessive body hair in women
what are the effects of anabolic steroid use on cholesterol?
increases LDL and decreases HDL
what is another name for kennedy’s disease? what is the cause?
spinobulbar muscular atrophy
LMN disease caused by mutation in androgen receptor by CAG repeat expansion (glutamine)
what is the result of the mutated receptor in kennedy’s disease?
toxic gain of function- degeneration of motor neurons in brain stem and spinal cord. muscle wasting by middle age (onset depends on number of repeats)
some signs of reduced androgen receptor function
describe the location of a sertoli cell and how they relate to germ cells.
span from basal lamina to lumen of seminiferous tubule
connected by tight junctions and surround developing germ cells.
describe the maturity of sperm as you move through the seminiferous tubule.
sperm are least mature near the basal lamina and most mature near the lumen of the tubule
at what stage does a sperm move into the lumen of the seminiferous tubule?
as a spermatid (after spermiation)
what does the spermatid mature into? what dose it require and how long does this take?
spermatozoa
testosterone
70 days
how are sperm activated?
by physiological changes in the female genital tract- become hyperactive
what does the acrosome of the spermatozoa do?
it offers protection and carries enzymes necessary to dissolve the jelly coat of the egg during fertilization
what glands produce the seminal plasmid and what is the concentration of sperm?
seminal vesicles, prostate gland and blubourethral glands
>20 million sperm/mL
what does the seminal vesicle produce?
70% of semen volume- large amount of fructose
what spinal segments provide the sympathetic innervation of the male genitalia and what does it cause?
T11-L2
responsible for emission and ejaculation. sympathetic tone maintains detumescence (sexual arousal)
what spinal segments provide parasympathetic innervation to the male genitalia and what is it responsible for?
S2-S4
corporeal vasodilation and smooth muscle relaxation leading to tumescence (erection)
where do the somatic and sensory aspects of penile control travel? what is the blood supply to the penis?
pudendal nerve
pudendal artery
which sympathetic plexi and nerves contribute to the penis?
mesenteric, hypogastric and pelvic plexi
hypogasteric and cavernous nerves
which parasympathetic plexi and nerves contribute to the penis?
pelvic plexus
pelvic nerve and cavernous nerve
what do nerve terminals of the PNS release on the penis? what is the result?
acetylcholine and nitric oxide
relaxes smooth muscle by increasing cGMP (NO)
acts through M3 receptors on endothelial cells to produce more NO (ACh)
how does viagra work?
inhibits cGMP- specific phosphodiesterase keeping cGMP levels high
stimulates erection only during arousal
describe the mechanics of erection
PNS fibers cause dilation of arteries, decrease in sympathetic tone (increased blood flow)
striated muscle contraction causing decreased venous flow and sinusoids of corora expand causing an erection
what veins are compressed in erection?
venous plexus and larger veins in the tunica albuginea
what are the mechanics of emission?
movement of ejaculate into urethra- SNS cuases contraction of smooth muscle of distal epididymis, vas deferens and accessory glands
what prevents sperm backflow?
internal sphincter of the bladder
what is anejaculation and what causes it?
inibility to ejaculate
sexual inhibition, medication, ANS malfunction, prostatectomy and ejaculatory duct obstruction
