LM 2.1: Hypothalamus-Pituitary Endocrine Axis

Question 1

what are the 2 main physiological functions that the hypothalamo-pituitary gonadal axis controls?

Answer 1

1. gametogenesis (oogenesis and spermatogenesis)
2. synthesis and secretion of male and female reproductive hormones: FSH, LH, estrogen, progesterone, testosterone, inhibit

Question 2

what is the clinical important of the HPG axis in health and disease processes?

Answer 2

1. growth
2. sexual development
3. metabolism
4. musculoskeletal build-up
5. strength
6. mood
7. energy
8. immune system
9. libido
10. reproduction

Question 3

what are the progressive stages of spermatogenic cells in the seminiferous tubule?

Answer 3

spermatogonia –> primary spermatocytes –> secondary spermatocytes –> spermatids –>

Question 4

where are sertoli and Leydig cells found?

Answer 4

Sertoli cells are present within the seminiferous tubules among spermatogenic cells for their substance.

Leydig cells are present outside the seminiferous tubule, and they produce testosterone.

Question 5

what are the steps in the HPG axis and feedback loop in males?

Answer 5

GnRH is produced in the preoptic nucleus of the hypothalamus in a pulsatile manner and is transported via portal veins to anterior pituitary gland

this causes release of LH and FSH from anterior pituitary

LH stimulates Leydig cells to synthesize and release testosterone

FSH stimulates Sertoli cells to synthesize and release ABP – ABP binds to T to maintain its high local concentrations in the testis since it’s essential for spermatogenesis

when high enough FSH levels have been reached in the serum, Sertoli cells release inhibin –> inhibin suppresses further release of FSH from the anterior pituitary

when high e tough testosterone levels have been reached in the serum and testis testosterone sends negative feedback messages to BOTH the hypothalamus and pituitary to suppress further release of GnRH and LH/FSH

Question 6

how do HPG hormones influence spermatogenesis?

Answer 6

GnRH in hypothalamus releases LH and FSH from anterior pituitary

LH (a.k.a Interstitial- cell- stimulating -hormone or ICSH in males) stimulates Leydig cells in testis to produce testosterone (which is an androgen). T is important for spermatogenesis, and for growth of Sertoli cells, which in turn support male germ cell development and survival.
IMPORTANT: -Without T, no spermatogenesis occurs.

FSH also acts on Sertoli cells to promote spermatogenesis

Sertoli cells provide growth- promoting nutrition to spermatozoa.

IMPORTANT: If Sertoli cells are disrupted, the spermatogenesis will not occur.

inhibin from Sertoli cells suppresses further production of FSH in pituitary through –ve feedback

Question 7

how does the HPG axis help with oogenesis?

Answer 7

ovaries send a +ve feed back to hypothalamus for release of GnRH

GNRH is released to stimulate FSH release from anterior pituitary which causes follicular growth/maturation and follicles increasingly produce E2 as they grow

once follicular growth is at its peak, E2 also peaks, triggering LRH release from hypothalamus, which in turn causes release of LH from pituitary and subsequently, ovulation

after ovulation Corpus Luteum (CL) forms which makes progesterone (P4).

high P4 and peak E2 together send -ve feedback to hypothalamus to stop FSHRH release, as well as to pituitary to stop further release of FSH; both E2 and P4 act to stop excessive FSH/ LH secretion

CL synthesizes progesterone (P4) and Estradiol (E2). Both are essential for maintenance of pregnancy – E2 and P4 suppress further release of GnRH

CL also produces relaxin and inhibin – inhibin works as a suppressor of further FSH release from the pituitary in females

Question 8

what happens to LH levels after ovulation?

Answer 8

LH level drops significantly but it continues to be produced in very low amounts in tonic form

this is because LH plays a role in promoting formation and growth of the corpus luteum but then once the placenta is formed, hCG replaces LHs role

Question 9

what is primary hypogonadism?

Answer 9

when the functioning of gonads is impaired because they do not respond to gonadotropins

testosterone and estrogen levels will be low because of testicular or ovarian failure

lowering of serum testosterone or E2 will result in high FSH/LH in the serum as a compensatory mechanism

this is why this condition is also known as hypergonadotropic hypogonadism

Question 10

what is an example of primary hypogonadism in females and males?

Answer 10

females: Turner syndrome
males: Klinefelter syndrome

Question 11

what is Turner syndrome? what will hormone levels be like?

Answer 11

a type of primary hypogonadism marked by premature ovarian failure; degeneration of follicles and death of oocytes soon after birth

serum FSH and LH will high since there are no estrogen secreting follicles left on the ovaries to produce Estrogen (E). Lack of E sends + feedback to hypothalamus and pituitary to release FSH / LH as a compensatory mechanism

Question 12

what is Kleinfelter syndrome? what will hormone levels be like?

Answer 12

a type of primary hypogonadism marked by low testicular growth

serum T levels will be low. Lack of T sends + feedback to hypothalamus and pituitary to release FSH / LH as a compensatory mechanism

Question 13

what is secondary hypogonadism?

Answer 13

when the gonads are secondarily affected by diseases that affect the hypothalamus or pituitary

there will be low levels of FSH, LH, estrogen and testosterone

Question 14

what are examples of secondary hypogonadism?

Answer 14

1. prolactinoma
2. Kallman syndrome
3. pituitary apoplexy

Question 15

what is a prolactinoma?

Answer 15

a type of secondary hypogonadism due to a pituitary tumor secreting prolactin

hyperprolactinemia inhibits GnRH which results in secondary hypogonadism meaning FSH and LH won’t be released resulting in hypogonadism

serum FSH and LH will be absent or very low

Question 16

what is Kallman syndrome?

Answer 16

a type of secondary hypogonadism due to a genetic mutation

marked by a lack of GnRH and a lack of sense of smell –> problems with puberty and anosmia

serum FSH and lH will be low due to absence of GnRH

Question 17

what is pituitary apoplexy?

Answer 17

a type of secondary hypogonadism caused by acute hemorrhagic infarction of pituitary glands

serum FSH and lH will be low

Question 18

what is functional hypothalamic amenorrhea?

Answer 18

absence or cessation of menses caused by a deficiency in the GnRH pulsatile secretion, resulting in failure of release of FSH and LH from pituitary, and downstream diminished estrogen production

it occurs in the absence of diseases of either gonads or pituitary glands – it’s a physiological deficiency even though the organs are normal

Question 19

what causes functional hypothalamic amenorrhea?

Answer 19

FHA is an amenorrhea that results from excessive calorie expenditure or low energy availability

this abnormal energy metabolism disrupts GnRH secretion

so FHA results from a functional ( physiological) disruption of GnRH due to disturbed metabolism

ex. athlete’s triad

Question 20

A 30-year-old man, reporting with infertility diagnosis, is confirmed to have a seller mass, visual defects, and higher than normal prolactin levels. Which one of the following is likely to occur and why?

A) Elevated prolactin levels are likely to decrease GnRH secretion from hypothalamus. The sperm production will remain unaffected.

B) Elevated prolactin levels are likely to increase GnRH secretion from hypothalamus which will in turn lead to downstream inhibition of testosterone synthesis and sperm production.

C) Elevated prolactin levels are likely to decrease GnRH secretion from hypothalamus and cause downstream inhibition of sperm production.

Answer 20

C) Elevated prolactin levels are likely to decrease GnRH secretion from hypothalamus and cause downstream inhibition of sperm production.

Question 21

A 15-year-old mentally challenged boy, with a history of normal puberty, accidently applies his dad’s testosterone jell to his skin over an 18 days period. Worried, his mom takes the boy to an endocrinologist’s clinic. Which one of the following completely describes the likely profile of his blood hormone levels?

A) Higher than normal FSH/ LH

B)
Higher than normal levels of testosterone

C)
Higher than normal FSH/ LH/ testosterone

D)
Higher than normal levels of testosterone and low serum FSH/ LH

Answer 21

D)

Higher than normal levels of testosterone and low serum FSH/ LH

Question 22

A 16-year-old girl, with normal signs of puberty at menarche, requires removal of her ovaries due a rare life-threatening granulosa cell tumor. Which one of the following scenarios will an endocrinologist most likely encounter when the girl is at age 25, and why?

A) Higher than normal FSH/ LH with normal estrogen levels

B)
Higher than normal levels of estrogen/ progesterone

C)
Higher than normal FSH/ LH/ estrogen

D)
Higher than normal FSH/ LH with very low or no estrogen

Answer 22

D)

Higher than normal FSH/ LH with very low or no estrogen

Question 23

A 27-year-old women, with abnormal menstrual cycles has been diagnosed with a Sella impacting pituitary prolactinoma. Administration of bromocriptine results in lowering of prolactin levels, and a return to normal release of GnRH. Which of the following is likely true in this scenario? Why?

A) FSH levels will be highly likely normal before treatment with bromocriptine.

B) FSH and LH levels are likely will remain unchanged.

C) Patient is unlikely to resume her normal cycles.

D) FSH levels are likely to return to normal after the treatment and menstrual cycle is likely to resume.

Answer 23

D) FSH levels are likely to return to normal after the treatment and menstrual cycle is likely to resume.

Question 24

A 43-year-old man has been diagnosed with prostate cancer with rising PSA levels. You know that the continued growth of prostate cancer cells depends on the androgen (testosterone, T). In order to achieve an androgen deprivation state, the oncologist team prescribes GnRH-antagonist treatment because of its GnRH nullifying effects. Which one of the following is likely to happen? Why?

A) GnRH levels in serum will increase, causing a direct lowering of T production by Leydig cells.

B) GnRH release from the hypothalamus will decrease, inhibiting the release of LH from pituitary. This will result in lowering of T production by Leydig cells. The net result of this will be androgen deprivation.

C) GnRH release from the hypothalamus will increase, causing increase in pituitary LH production, and a subsequent lowering of T.

Answer 24

B) GnRH release from the hypothalamus will decrease, inhibiting the release of LH from pituitary. This will result in lowering of T production by Leydig cells. The net result of this will be androgen deprivation.