Endocrinology of Male

Question 1

Hypothalamus-Pituitary-Testis Axis

Answer 1

– ONLY negative feedback
o Hypothalamus produces LHRH in the medial preoptic area and arcuate nucleus
 This region is larger in males than females
o LHRH stimulates release of LH and FSH in the anterior pituitary
o LH binds to receptors on Leydig cells in testes and stimulates production of testosterone
 Testosterone has SHORT loop negative feedback on anterior pituitary (inhibit LH)
 Testosterone has LONG loop negative feedback on hypothalamus (inhibit LHRH)
o FSH binds to Sertoli cells and stimulates spermatogenesis (production of sperm cells)
 Sertoli cells produce inhibin that is involved with negative feedback
• SHORT loop negative feedback – on anterior pituitary (inhibit (FSH)
• LONG loop negative feedback – on hypothalamus (inhibit LHRH)

Question 2

Inhibin

Answer 2

– secreted by Sertoli cells for negative feedback of FSH
o Alpha and beta (A & B) subunits
 Alpha + Beta-A = Inhibin A – marker for ovarian cancer
 Alpha + Beta-B = Inhibin B – most common – inhibits FSH; little action on LH
• testing male infertility
 Beta-B + Beta-B = Activin – stimulates FSH production and local effects
o Circulatory pattern in LH and testosterone levels suggest inhibin may have inhibitory effects on LH too

Question 3

Lh Effects on Leydig Cells

Answer 3

o LH binds to membrane receptor  G protein  increases cAMP  internal messengers activate cychrome p450 enzyme to convert cholesterol into testosteron

Question 4

Testosterone in Circulation

Answer 4

o	Hydrophilic substance – therefore must bind to testosterone binding proteins (or sex-steroid hormones) or albumin when in circulation
o	Unbound (3%) testosterone is what exerts its effects

Question 5

Testosterone Effects Mechanisms

Answer 5

o Diffusing directly through the cell membrane and attaching to intracellular androgen receptors
 Androgen receptors located in cytoplasm or already bound to chromatin
 Alter mRNA production to develop certain proteins
 Ex: tissues of penis – testosterone binds and penis produces proteins that allow it to grow
o Converted to estrogen
 Some cells have their own aromatase enzyme doing this conversion
 Ex: fat cells and neurons
o Converted to dihydroxytestosterone (DHT) – more potent form of testosterone
 5-alpha-reductase does the conversion
 Binds to androgen receptors with much greater affinity than testosterone
 Ex: prostate, hair follicles
o Effect extracellular membrane receptor to act on the internal system
 Testosterone binds to surface receptor and causes changes intracellularly

Question 6

Major Effects of Testosterone

Answer 6

o Fetal development of Internal male organs - epididymis, vas deferens, and seminal vesicles
o Pubertal growth of penis, seminal vesicles, musculature, skeleton, larynx(for manly voice)
o Spermatogenesis

Question 7

Major Effects of DHT

Answer 7

o Fetal development of External male organs - penis, penile urethra, scrotum, prostate
o Pubertal growth of scrotum, prostate, sexual hair, sebaceous glands (skin glands that produce oil)
o Prostatic secretion

Question 8

Fetal Life

Answer 8

o Testosterone spike at ~2 months in development as a result of hCG
 Targets fetal Leydig cells to produce testosterone for male sex organ development
 Activates hypothalamus (increase glutamate and decrease GABA neurotransmitters)
• Develops proper feedback mechanisms so preoptic arcuate nucleus will only respond to negative feedback and never positive (like women)
 Help develop gender self-identity and gender preference
o Levels drop when hCG decreases due to placental development

Question 9

Birth

Answer 9

o Shortly after birth there’s a spike in testosterone stimulated by LH and FSH
 Plays role in descending the testes
o After birth, hypothalamus is very sensitive to testosterone; any small increase results in negative feedback on LHRH

Question 10

Puberty

Answer 10

o All-time low FSH, LH, and testosterone prior to puberty
o Around puberty, hypothalamus desensitization to negative feedback allows the levels of testosterone to rise RESETTING THE GONODOSTAT
 Glutamate gets activated and GABA is deactivated
 Larger and larger amounts of LH/FSH produced because of no negative feedback  increase in testosterone

Question 11

Old Age

Answer 11

o Testosterone levels remain high consistently until the age of 60
o After 60 testosterone levels gradually decreases but never completely off

Question 12

Kallmann’s

Answer 12

o Failure of migration of LHRH neurons to move from olfactory bulb to hypothalamus in embryo
o Resulting in low or no LHRH secretion and thus testosterone
o Improper virilization  male with small penis and scrotum, small muscle development in shoulders, fat accumulation in hips, low amount of sexual hair
o Shy, timid demeanor
o Poor sense of smell
o Mechanism: failure of migration in LH and FSH cells from olfactory tissue
o Treatment: give testosterone and above conditions should reverse

Question 13

Precocious Puberty

Answer 13

o Early onset puberty (such as 2 years old) resulting in being large for his age with increased size of testes and penis, with some pubic hair growth
o Mechanism: tumor, brain injury, natural variance in puberty development, variations
o Treatment: give LHRH superagonsits to down regulate gonadotrophic cells (decrease LH and FSH production) until the age of 13

Question 14

Androgen Resistance Syndrome (Androgen Insensitivity Syndrome; Testicular Feminization Syndrome)

Answer 14

o Androgen receptors are defective
o XY males but body never experiences testosterone so their bodies are feminized
 Internal testes do not descend
 Blind-ended vagina (does not lead to uterus)
 LOOK female and sometimes little on tall side
o Mechanism: genetics
o Treatment: difficult because person most likely would identify as female up to this point in life