SM182 Endo Control of Female Reproduction I

Question 1

HPG axis

Answer 1

GnRH (hypothalamus) -> LH/FSH (anterior pituitary) -> Steroidogenesis (ovary)

E2: negative and positive (LH surge) feedback
P: negative feedback
Inhibin A and B: negative feedback

Question 2

4 unique features of endocrine control of reproduction

Answer 2

1) pulsatile secretion of GnRH
2) pulsatile GnRH secretion is required for proper regulation of LH and FSH
3) LH and FSH are made by the same cell (gandotrope)
4) positive hormonal feedback by E2

Question 3

GnRH neuron location, embryonic development

Answer 3

Arcuate nucleus of the medial basal hypothalamus

Migrate with the olfactory placed during fetal development (Kallmann’s syndrome)

Question 4

Gonadotropes

Answer 4

Anterior pituitary cells that secrete FSH and LH

Question 5

FSH and LH structure comparison

Answer 5

Share a common alpha subunit (as well as with TSH and hCG), have different beta subunits

Question 6

LH actions

Answer 6

Stimulates A and T production by the ovarian Theca cells

After ovulation, stimulates P production by the granulosa-lutein cells of the corpus luteum and inhibit Inhibin A production

Question 7

FSH actions

Answer 7

Regulates E2 production by stimulating ovarian follicle granulosa cell growth and aromatase activity as well as Inhibin B production

Question 8

Follicle cell types and actions

Answer 8

Theca: produce androgens and pass them to the granulosa cells

Granulosa: contain aromatase, turn A and T into E

Question 9

Uterine hormone response

Answer 9

Very sensitive to E2 and P, shedding occurs after withdrawal of these during menses

Regenerates in response to E2

Question 10

Two-cell hypothesis of ovarian steroidogenesis

Answer 10

LH stimulates theca cells to produce androgens, primarily A, which diffuse to granulosa cells

FSH stimulates granulosa cell growth and aromatase activity

Question 11

Aromatase: locations, actions

Answer 11

Adipose tissue, breast, CNS, granulosa cells: converts A and T to E1 and E2

Question 12

17-beta hydroxysteroid dehydrogenase (17bHSD): actions

Answer 12

Converts A to T and E1 to E2

Question 13

5-alpha reductase: location and actions

Answer 13

Androgen-sensitive tissues, such as the pilosabeceous unit

Converts T to the more potent DHT

Question 14

Androgen receptor type

Answer 14

Nuclear receptor

Question 15

Sex hormone binding globulin (SHBG): hormones bound and affinity, action, hepatic regulation

Answer 15

High affinity binding protein for estrogens and androgens (A > E)

When bound, hormones are inactive (active when free or associated with albumin)

Hepatic production stimulated by estrogen and thyroid hormone, inhibited by androgens, obesity, and insulin

Question 16

Inhibin A & B: structure, action, source

Answer 16

Heterodimer consisting of an alpha and betaA or betaB subunit (form inhibin A and inhibin B, respectively)

Inhibit FSH release (endocrine)

A: both granulosa and theca cells
B: secreted by granulosa cells of small antral follicles

Question 17

Activin: structure, action, source

Answer 17

Homodimer of inhibin-beta subunits

Stimulate FSH release (autocrine/paracrine)

Pituitary and ovary

Question 18

Follistatin: action

Answer 18

Inhibits FSH release by binding and neutralizing activin (autocrine/paracrine)

Question 19

GnRH pulse generator

Answer 19

Necessary to maintain gonadotrope responsiveness to GnRH

Continuous delivery suppresses gonadotropin secretion

Question 20

Puberty

Answer 20

Sleep-dependent onset of pulsatile GnRH secretion

Before puberty, CNS restricts release

Question 21

GnRH pulse frequency: fast and slow

Answer 21

Modulates gonadotropin secretion

Fast: LH

Slow: FSH

Question 22

GnRH feedback response: E2

Answer 22

Slows pulse frequency

OR

Positive feedback is necessary for the LH surge and ovulation

Question 23

GnRH feedback response: P

Answer 23

Slows pulse frequency

Question 24

Menarche

Answer 24

~13

Has started occurring earlier over the past few centuries

Question 25

Adrenarche

Answer 25

Development of the zone reticularis, release of androgens resulting DHEAS and development of pubic and axillary hair

6-8 years

Question 26

Ovarian follicular development

Answer 26

Preantral follicle development is gonadotropin-independent and regulated by intraovarian factors

Maturation of follicles occurs with resumption of meiosis, which requires FSH and LH

A single dominant follicle emerges 5-7 days after the start of menses, the rest become atretic

Question 27

Follicular phase of menstrual cycle: early, mid, and late

Answer 27

Period prior to ovulation

Early: FSH increase persists from the end of the last cycle, dominant follicle is selected, LH pulse frequency increases in the absence of E2 and P negative feedback and stimulates theca cells to produce T, which is aromatized into E2 in granulosa cells. Inhibin B increases follicular growth.

Mid: GnRH pulse frequency increases in synergy with increasing ovarian E2. Inhibin B production suppresses FSH release.

Late: continued increase in E2 production induces mid-cycle LH surge, which induces ovulation of the dominant follicle.

Question 28

Luteal phase of menstrual cycle

Answer 28

Period after ovulation

Post-ovulatory follicle luteinizes, forming the corpus luteum and beginning to secrete P and E2. These hormones feedback to slow GnRH pulse frequency. FSH release selectively increases and LH release decreases.

The increase in FSH stimulates follicular recruitment for the next cycle in case no fertilization occurs. P production falls as LH decreases and stops if not rescued by P from the embryo.

Menses occurs with the fall of P and E2.

Question 29

Endometrium: proliferation

Answer 29

E2 (or synthetic estrogens from OCPs) stimulate proliferation of endometrial stromal and epithelial cells

Also induce the express of P receptors

Ability to respond to P depends on estrogen-induced P receptor expression

Question 30

Endometrium: differentiation

Answer 30

P (or synthetic progestins) induce differentiation of the proliferative endometrium

P also prepares the endometrium for implantation of the embryo

Question 31

Endometrium: menstruation

Answer 31

In the absence of hCG from the embryo, P and E2 production from the corpus luteum stops, leading to vasomotor changes that cause lining shedding

Question 32

Menopause

Answer 32

51-52 years

Ovarian estradiol production stops, but ovarian androgen production continues for a few years. These can get aromatized to E extragonadally (fat)