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Flashcards in Female Physiology Deck (40):
1

Maturation of primary oocyte

During puberty, primary oocytes undergo change into secondary oocyte (arrested in metaphase II) --> dependent on the LH surge
- once fertilization occurs --> secondary oocyte undergoes Meiosis II and becomes an ovum

2

Corpus Luteum

produces progesterone --> silences the ovary and remains patent until either 2nd trimester of pregnancy or it involutes if no fertilization occurs

3

Summary of Ovarian Follicular Development

1. Birth --> all oogonia developed into primary oocytes
2. Primary oocytes surrounded by follicular cells = granulosa/thecal cells (primordial follicles)
3. Primordial follicles slowly progress to primary follicles
4. When follicles exhausted = menopause
5. Each cycle, a cohort of follicles recruited and usually one becomes ovulatory follicle
6. Recruitment refers to antral follicles stimulated by FSH
7. Dominant follicle is largest and produces most hormones

4

Hypothalamo-Pituitary Ovarian Axis

- Hourly GnRH pulses result in FSH and LH basal secretion
- FSH stimulates follicle development
- FSH/LH promotes estrogen synthesis
- Estrogen feedbacks negatively to hypothalamus and pituitary --> reduces FSH and LH
- Inhibin inhibits FSH secretion, no effect on LH

5

Feedback of estrogen and secretions

- Feedback relationship between estrogen and secretions reverse when antral follicles are large --> high estrogen induces rapid GnRH pulses and ovulatory surge in LH
- Inhibin levels increase as well to keep FSH in check --> reducing more follicle development

6

GnRH

polypeptide hormone
- produced in arcuate nucleus of hypothalamus
- pulsatile secretion
- member of Gq --> increased Ca

7

FSH

follicular growth and estradiol secretion

8

LH

critical for inducing ovulation
ovulation required for formation of corpus luteum

9

hCG

1st trimester maintains the corpus luteum -> which keeps progesterone levels high to maintain pregnancy
- later in pregnancy the placenta takes over

10

FSH, LH, hCG

secretions are cyclical --> essential for normal gonadal response
- serum [ ] increase with removal of ovaries and when ovarian functions decrease

11

FSH, LH, hCG receptors

Gs protein coupled --> increase cAMP
LH/CH receptors are in thecal cells --> androgen production
FSH receptors are in granulosa cells -> converts androgens to estrogen (estradiol 17beta)

12

Estrogen receptor

ERalpha --> mediates HPO axis response to estrogen
- SHBG = steroid hormone binding globulin

13

Menstrual Cycle

1. Small increases in LH and FSH lead to follicular growth --> increase synthesis and secretion of ovarian steroids
2. High levels of estrogen provoke changes in GnRH to manifest rapid pulses
3. Stimulates surge of LH which induces resumption of meiosis
4. Ovulation induces luteinization --> corpus luteum
5. If no conceptus -> spontaneous luteinolysis

14

Ovarian Cycle

Estrogen = thickening and proliferation of endometrium
Progesterone = halts further growth of endometrium

15

Maternal recognition of pregnancy

hCG produced by chorion --> maintains/promotes maintenance of corpus luteum

16

Maintenance of pregnancy

accomplished by placenta

17

Endocrine control of pregnancy

Shifts from P>E to E>P
Progesterone causes hyperpolarization of myometrial cells --> prevent contractions, inhibits oxytocin receptor synthesis, inhibits ER synthesis
Estrogen causes increase oxytocin receptors, promotes uterine contractility, cervical ripening, increases local PG release from placenta

18

Prostaglandins

PGF2 and PGE are predominant in reproduction
- involved in rupture of Graafian follicle at ovulation
- primes the uterus for real deal

19

Oxytocin

secreted from posterior pituitary
- main effects are on uterus and breast during childbirth and lactation
- (+) autoregulation within hypothalamus during labor

20

Breast Development

Puberty -> development of ductal tree (estrogen, glucocorticoids, and GH dependent)
Pregnancy -> mid-late preg (lobular-alveolar growth), post-partum (copious milk secretion, removal of placenta -> prolactin dependent)

21

Lactation

Galactopoiesis -> presence of prolactin and removal of milk
Milk Ejection -> oxytocin
Involution -> lack of prolactin or suckling

22

Folliculogenesis promotion

FSH and LH for women with hypothalamic anovulatory function
Clomiphene citrate (estrogen antagonist) for women with endogeneous estrogen activity and normal HPO function

23

Mimic gonadotropins

Menotropins -> pergonal with hCG given in sequence for ovulation in anovulatory women and production of multiple follicles
Urofolitropin -> metrodin with hCG given in sequence for induction of ovulation of patients with PCOD
Follitropin -> induce follicle development and when coupled with hCG -> induction of ovulation

24

*Clomiphene Citrate*

Estrogen antagonist (Selective estrogen receptor modulator)
- blocks ER signaling to hypothalamus and anterior pituitary -> stimulates release of GnRH and gonadotropins
- used as fertility drug to induce ovulation

25

2 Step ovulation induction

1. Follicular Stimulation using combined FSH and LH
2. hCG stimulates LH surge -> follicular maturation and ovulation

26

hCG (human chorionic gonadotropin)

isolated from urine in pregnant women
- binds to LH/CG receptor -> LH-like induction of ovulation
- stimulates estrogen primed follicle to induce meiotic resumption

27

GnRH Agonists

Synthetic GnRH -> Leuprolide
- nonpulsatile administration -> suppresses FSH and LH (AFTER initial transient rise) --> shuts down HPO
- pulsatile administration -> release of FSH/LH -> inducing follicle development

28

GnRH Antagonists

Ganirelix, Cetrorelix
- competitive antagonist of GnRH -> suppressing gonadotropin release
- used in fertility to prevent LH surge while promoting folliculogenesis
- used in prostate and breast cancer therapy to inhibit steroid production
*No transient rise in FSH, LH

29

Effects of Estrogens

development, growth, maintenance of sex tissue
skeletal growth, body shape
key regulator of HPO axis and maintaing menstrual cycle

30

Uses of estrogen

Oral contraceptives, HRT, dysmenorrhea

31

Estradiol 17beta

PRINCIPAL NATURAL HORMONE
- readily absorbed, 1st pass metabolism limits oral effectiveness --> addition of methyl at 17 reduces metabolism
- injection, patch, gel, vaginal ring

32

Tamoxifen

Estrogen antagonist in breast and vasculature
Agonist in uterus, bone, lipoproteins
SERM

33

Raloxifene

SERM
Agonist - bone, lipoproteins
Antagonist - breast, uterus (ER+ breast cancer)

34

Toremifene

SERM
Antagonist - breast
no effect in bone
Agonist - uterus

35

Fulvestrant

SERD (down regulator)
- PURE estrogen antagonist -> blocks receptor binding and down regulates receptor in all tissues

36

Aromatase inhibitors

steroidal and nonreversible -> exemestane
nonsteroidal and reversible -> anastrozole, letrozole
treat ER+ cancer

37

Actions of progesterone

development and maintenance of secretory endometrium
- promotes uterine relaxation during pregnancy
- withdrawal during late pregnancy is part of partruition
- prepares breast for lactation

38

Uses of synthetic progestins

Oral contraceptives, HRT, dysmenorrhea, luteal supprt

39

Synthetic Progestins

Progestanes -> medroxyprogesterone acetate
Estranes -> norethindrone
Gonanes -> levonorgestrel (more potent at lower doses)
- 17alpha substitution decreases 1st pass metabolism

40

Emergency contraception

Levonogestrel -> progesterone agonist
Mifepristone (also abortefacient) and Ulipristal acetate -> progesterone antagonist
MOA - interferes with ovulation as emergency contraception