neuroendocrine axis and feedback mechanisms

Question 1

hypothalamus pituitary target axes

the hypothalamic control of what gland underlies the ability of mammals to coordinate endocrine functions

Answer 1

pituitary gland

Question 2

GnRH

• what 10-amino acid hypothalamic neuropeptide controls the function of the reproductive axis?

Answer 2

GnRH

Question 3

GnRH

neurons of which nuclei of the hypothalamus release GnRH?

Answer 3

neurones of the arcuate and preoptic nuclei

Question 4

GnRH

what does GnRH stimulate through the hypophyseal portal system and from what place

Answer 4

stimulates:
- LH
- FSH

from anterior pituitary

Question 5

GnRH

how what type of secretion is GnRH secretion and what does this type of secretion govern?

Answer 5

• pulsatile
• governs release of pituitary gonadotrophins

Question 6

GnRH

what are 3 factors that can influence GnRH secretion?

Answer 6

-stress
- exercise
- diet

Question 7

GnRH

at what age is GnRH detectable in the hypothalamus and when is FSH and LH produced

Answer 7

• 10 weeks gestational age
• FSH and LH starts production between week 10-13

Question 8

GnRH pulsatility

• what 5 upstream hormonal and neural pathways GnRH neurons are controlled

Answer 8

• morphological changes in GnRH neurones
• inhibitory and excitory afferent signals form distinct neurotransmitters
• the Kisspeptin-neurokinin b-dynorphin (kndy) neuronal network
• steroids negative feedback
• nutrition and metabolism

Question 9

gonadotropins

Name the 2 main gonadotropins and what cells secrete them

Answer 9

• FSH and LH
• gonadotrophic cells under control of the HPG (HPO/HPT) axis

Question 10

hypothalamic control

what does more rapid GnRH pulse frequencies favour?

Answer 10

favours LH secretion

Question 11

hypothalamic control

what does slower GnRH pulse frequencies favour?

Answer 11

favours FSH secretion

Question 12

peptide hormones

what are inhibins and where are they produced in males and in females

think FSHb subunit for first part

Answer 12

• circulating endocrine hormones originating in gonads that act on the pituitary to speficially inhibit expression of the FSHb subunit

Males:
- produced in sertoli cells in testes

females:
- produced in ovarian follicles

Question 13

peptide hormones

what are activins and where are they produced

Answer 13

potent stimulatory effectors of FSH expression

• produced in the gonads and in the pituitary gland

Question 14

peptide hormones

what is follistatin and what pule frequency increases the expresson of follistatin

Answer 14

• potential inhibitor of FSHb expression and secretion that works with inhibin.
• high frequency GnRH pulses

Question 15

sex steroids

What 2 ways do Gonadal steroids control gonadotropins

Answer 15

• regulating GnRH expression
• regulating the production of gonadotropins directly

Question 16

Gonads control: MALE

outline the 6 stage process of Gonadal control in males

Answer 16

1. GnRH from hypothalamus stimulates secretion of LH and FSH from anterior pituitary
2. LH stimulates testosterone secretion from interstitial cells
3. FSH stimulates sertoli cells in seminiferous tubules to increase spermatogenesis and secrete inhibin
4. testosterone has stimulatory effects on sertoli cells and on the development of reproductive organs, and secondary sexual characteristics
5. testosterone causes a negative feedback efect on hypothalamus and pituitary, reducing GnRH, LH and FSH secretion
6. inhibin has negative feedback effect on anterior pituitary, reducing FSH secretion

Question 17

HPG axis control: follicular phase

outline the HPG axis control in the follicular (proliferative) phase of the menstrual cycle

Answer 17

1. GnRH release from hypothalamus acts on Anterior pituitary causing FSH and LH secretion
2. LH acts on theca cells to induce androstenedione. Androstenedione is converted to oestradiol by aromatase from granulosa cells after FSH stimulation
3. as follicles grow they release more oestrogens, which inhibits the secretion of LH and FSH by acting on the Hypothalamus to decrease GnRH secretion

Question 18

HPG axis control: ovulation

outline the HPG axis of control in ovulation phase of the menstrual cycle

Answer 18

1. 2 days before ovulation, granulosa cells begin to develop LH receptors alongside the existing FSH receptors
2. As the dominant follicle keeps secreting oestrogen, the rising oestrogen levels make teh pituitary galnd more responsive to GnRH
3. This creates a positive feedback loop triggering a mid cycle ovulatory surge of LH and FSH secretion
4. the increased LH and FSH acts on Granulosa and theca to facilitate the rupture of the follicle and the release of the oocyte, leading to ovulation

Question 19

HPG axis control: Luteal phase

outline the HPG axis of control for the luteal (secretory) phase of the menstrual cycle

Answer 19

1. LH levels are high after rupture of follicle, and remains of follicle becomes corpus luteum.
2. Luteinized thca cells respond to low concentrations of LH by producing progesterone. Luteinized granulosa cells secret inhibin which inhibits secretion of FSH from pituitary gland
3. As oestrogen levels decrease, progesterone levels increase, making the endometrium receptive to the implantation of a fertilised gamete and causes negative feedback on the pituitary gland.
4. Remaining oestrogens effect the anterior pituitary gland to decrease the secretion of FSH and LH
5. if implantation doesnt happen, corpus luteum becomes corpus albicans, leading to no hormone production and a collapse of spiral arteries. this in turn leads to menstruation.