Male Reproductive Endocrinology (2) Flashcards
What makes someone a gonadal male?
SRY gene encodes testis determining factor
What makes someone genotypically a male?
Y chromosome
What is TDF?
A transcription factor
What makes someone phenotypically male?
Hormones produced by the gonads determine the phenotypic sex
When can an XX male occur?
In rare cases when the SRY gene translocates to the X chromosome during male meiosis
What determines the fate of primordial gonads?
Te genotype of the germ cells that the primordial gonads contain
In males, what do mesonephors develop into?
Epididymis
What is an indifferent gonad closely associated with?
Mesonephros and wolffian duct
What do leydig cells promote?
Androgens
What do androgens help promote development of?
- Wollfian ducts and derived internal genitalia —> requires testosterone
- Prostate development —> requires DHT
What type of external generalist develop in the absence of testosterone?
Female
Is testosterone or DHT responsible for the development of mLe external genitalia?
Testosterone is converted to DHT….this then stimulates differentiation into male external genitalia
Hat type of receptor does GnRH bind? What are its actions?
G protein coupled gonadotropin receptor and it then activates PLC to increase Ca++, DAG production and PKC activation
Describe GnRH release and LH/ FSH release?
Pulsation
What do constant levels of GnRH lead to? What are the clinical applications of this?
Inability to release LH and FSH…this is a treatment for prostate cancer in an effort to lower testosterone production.
In the prenatal stage, what is the source of sex-steroid production in the testes?
Leydig cells….which increase in number in a manner dependent on maternal chorionic gonadotropin or embryonic leutenizing hormone.
Prior to puberty, describe GnRH/ LH/ FSH pulses and levels and describe the axis sensitivity to negative feedback?
- Few GnRH pulses
- Low LH and FSH levels
- The axis is VERY sensitive to negative feedback inhibition by androgens
During puberty, describe GnRH/ LH/ FSH pulses and levels and describe the axis sensitivity to negative feedback?
Frequency and amplitude of GnRH pulses increase
LH and FSH production increase
Sensitivity to negative feedback of testosterone decreases
What type of cells does FSH stimulate?
Sertoli
What type of cells does LH stimulate?
Leydig cells
Which cells produce inhibit and where does inhibit act?
Sertoli cells produce inhibit which feeds back to the anterior pituitary to decrease release of FSH
How does testosterone effect sertolic cells?
Activate Sertoli cells
When LH stimulates it’s target cell, what are the transcriptional changes made?
Increased transcription of:
- enzymes involved in testosterone synthesis
- enzyme for RLS of steroid hormone synthesis
- sterol carrier protein and sterol activating protein
When FSH stimulates it’s target cell, what are the transcriptional changes made?
Increased transcription of:
- androgen binding protein
- aromatase enzyme
- growth factors (to support production of sperm)
- inhibits
True or false: inhibits suppress leydig cell proliferation
True
What do leydig cells produce that inhibits Sertoli cells?
Beta- endorphin
What do Sertoli cells produce that can stimulate leydig cells?
Estrogen
What is lacking in Kallmann syndrome?
Lack of pituitary hormones LH and FSH because lack GnRH
What is the explanation for why people with Kallmanns syndrome can’t smell?
The olfactory receptors and the GnRH secreting cells both develop in the olfactory epithelium and then the GnRH secreting cells migrate into the brain
Name the enzyme and where it is found:
Cholesterone ————–> Pregnenolone
Desmolase
Leydig cells
Where is aromatase found? What does it do?
Sertoli cells
Testosterone/ androstedione ——–> estradiol/ estrone
Name the enzyme:
Testosterone ——-> DHT
5- alpha- reducatse
Name two causes of male psuedohermaphroditism:
5alpha reducatse deficiency and androgen insensitivity syndrome
What are some anabolic effects of androgens?
Promote protein synthesis, growth in muscle and strength, increased bone density/ strength/ linear growth
Are FSH levels higher in females?
No, they are 8x higher in males
Which androgen is responsible for the following:
Sebum formation, beard growth, prostate development, external genitalia, sperm production, sex drive/ behavior, feedback inhibition to hypothalamus
DHT
Which androgen is responsible for:
Increased RBC, increased muscle mass, increased upper body fat, increased VLDL, increased LDL, decreased HDL, sperm production
Testosterone
Which androgen is responsible for the following:
Sperm production, skeleton maturation, sexual behavior
Estradiol
Describe the changes in male senescence:
NO abrupt loss of fertility
Testosterone decreases starting at age 30
Quantity/ quality of sperm decreases
FSH/ LH levels increase
What is used to treat male pattern baldness?
Finasteride, which blocks the production of DHT
What are the effects of anabolic steroid use:
Reduction in sperm count, shrunken testicles
Damage to heart, liver, kidneys, psych problems
Breast enlargement
What is defective in spinobulbsr muscular atrophy?
LMN disease caused by mutation in the androgen receptor because of a CAG repeat which leads to a polyglots mine expansion
What initiates spermatogenesis?
Initiated at puberty through the action of FSH and LH
Percentage of sperm in semen?
10%
After spermiation, where do spermatids move?
They move passively into rete testes and epididymis
What is maturation is sperm dependent on?
Testosterone
The flaccid penis is under SNS or PNS control?
SNS
Is the SNS or PNS responsible for erection?
PNS
What is the action of Viagra?
Inhibits a decrease in CAMP, keeping the levels high, by inhibiting cAMP specific phosphodiesterase
What NTs are involved in erection?
NO and ACh
Does SNS or PNs control emission?
SNS