Male Reproductive Endocrinology Flashcards
What is required for the development of testes and germ cells to develop into spematogonia?
SRY
What is required for the external genitalia to develop?
dihydrotestosterone (DHT)
How does XX male occur?
SRY gene translocates to X chromosome during male meiosis—testis determining factor (TDF) is put on males X chromosome–XY Female can occur if TDF is absent from Y chromosome
Androgens produced by Leydig cells promote what?
Differentiation of the Wolffian (mesonephric) duct–Requires testosterone—NOT DHT
Prostate development—REQUIRES DHT
What causes Mullerian ducts to degenerate?
Anti-Mullerian hormone released from Sertoli cells
What do the mesonephros develop into in males?
epididymis
What does the Wolffian duct develop into in males?
vas deferens
seminal vesicles
ejaculatory duct
What happens to the Mullerian ducts in males and in females?
Degenerate in males
form the fallopian tubes/uterus/cervix in females
What does constant release of GnRH cause?
What can this treat?
Prevents LH and FSH release
Downregulation of receptors
Prostate cancer–to lower testosterone production
What is the mechanism for GnRH activation?
GCPR –gonadotroph receptor–activates PLC–release Ca–DAG and PKC activation
What is the increase in Leydig cells dependent on?
maternal chorionic gonadotropin (hCG)–early development
embryonic LH–late development
Prior to puberty how is hormones levels maintained at a low level?
Few GnRH pulses–low FSH and LH levels
Hypothalamus and pituitary–very sensitive to negative feedback inhibition by androgens
What occurs at puberty?
Frequency and amplitude of GnRH pulses increase
Sensitivity of H-P axis to negative feedback of testosterone decreases
Gonadotroph sensitivity to GnRH increases
LH and FSH production increases
Testosterone increases and spermatogenesis begins
Androgen-driven changes characteristic of puberty occur
What does LH bind to stimulate production of testosterone?
Leydig cells
What does FSH bind and what proteins are produced from this binding?
Sertoli cells
ABP/aromatase/growth factor/inhibin
What inhibits release of GnRH from the hypothalamus?
testosterone neg feedback
What inhibits FSH release from the anterior pituitary?
Inhibin neg feedback
Stimulation of Leydig cells with LH occurs how and what does this cause?
GPCR–cAMP–PKA
Increases transcription of
- Enzymes involved in testosterone synthesis
- Stimulates rate-limiting step (cholesterol to pregnenolone) in testosterone synthesis
- Sterol carrier protein and sterol activating protein synthesis
Stimulation of Sertoli cells by FSH occurs how and what does this cause?
GPCR–cAMP–PKA
Increases transcription of
- androgen binding protein–keeps testosterone levels high
- P450 aromatase–produces estrogen
- growth factors–support sperm production
- inhibin- suppress Leydig cell proliferation/suppress FSH secretion
Also has secondary effects on Leydig cells and sperm (increases motility)
What do Leydig cells produce that act on Sertoli cells?
Testosterone
B-endorphin–which inhibit Steroli cell proliferation
What do Sertoli cells convert testosterone to that acts on Leydig cells?
Estradiol
What is Kallmann Syndrome?
Mutation causing congenital anosmia (complete inability to smell) and failure to enter puberty—Main danger is osteoporosis
hypogonadotropic hypogonadism–GnRH neurons and olfactory neurons have same developmental origin
What is the rate limiting step of testosterone production and where/how does it occur?
Cholesterol—>pregnenolone occurs in the mitochondria through P450 side chain cleavage enzyme–Desmolase–removes side chain of cholesterol
What does 5a reductase deficiency cause?
Male Pseudohermaphroditism–DHT levels reduced—failure of development of urogenital sinus and external genitalia
