Reproductive Hormones B&B

Question 1

how are reproductive hormones transported through the body?

Answer 1

carried by sex hormone binding globulins (SHBGs), and to a smaller extent by albumin

SHBGs are glycoproteins synthesized by the liver, bind androgens&raquo_space;» estrogens

Question 2

what is the significance of sex hormone binding globulins (SHBGs) preferentially binding androgens over estrogens?

Answer 2

recall free/unbound hormones exert clinical effects

when there is an increase in SHBGs, the effect is greater on androgens —> “estrogen amplification”

high SHBGs can cause gynecomastia in men, low SHBGs can cause hirsutism in women

Question 3

what are some causes of high vs low sex hormone binding globulins (SHBGs)?

Answer 3

increase SHBG: estrogen (ex, birth control), hyperthyroidism —> estrogen amplification —> gynecomastia in men

decrease SHBG: androgens, hypothyroidism, nephrotic syndrome (protein lost in urine) —> androgen amplification —> hirsutism in women

recall SHBG bind androgens&raquo_space; estrogens (and only free hormones are active)

Question 4

explain why patients with cirrhosis exhibit clinical features of high estrogens/low androgens

Answer 4

cirrhosis disrupts the metabolism/excretion of estrogen, and estrogen causes an increase in sex hormone binding globulins (SHBGs)

SHBGs bind androgens&raquo_space; estrogens… therefore, there is a decrease in free androgens

—> gynecomastia, spider nevi (skin), palmar erythema, testicular atrophy, impotence

Question 5

what cell signaling pathway does GnRH (gonadotropin releasing hormone) activate?

Answer 5

GnRH (hypothalamus) binds receptors on anterior pituitary —> activates Gq protein with IP3 second messenger

1. PIP2 split into IP3 and DAG
2. IP3 causes Ca2+ release from ER
3. Ca2+ activates DAG
4. DAG activates PKC

Question 6

leuprolide

Answer 6

leuprolide: GnRH agonist with D-amino acid substitution to make it resistant to degradation (increase t1/2)

can act as agonist and antagonist! chronic tx causes down-regulation of GnRH (pituitary desensitization)

Question 7

Kallmann Syndrome

Answer 7

lack of GnRH neurons in the hypothalamus (due to impaired migration from olfactory bulb)

almost always in males —> low FSH, LH, testosterone

—> hypogonadism and anosmia (loss of smell, key word giveaway!!)

Question 8

A 14yo M is presenting with delayed puberty and anosmia - what is the likely diagnosis?

Answer 8

Kallmann Syndrome: lack of GnRH neurons in the hypothalamus (due to impaired migration from olfactory bulb)

almost always in males —> low FSH, LH, testosterone

—> hypogonadism and anosmia (loss of smell, key word giveaway!!)