Female

Question 1

Genetic Sex is determined at conception

Answer 1

46 XY is genetic male and 46 XX is genetic female, In general, lack of hormonal signals leads to a female phenotype and hormones are required to develop the male phenotype

the absence of the Y chromosome leads to the development of the ovaries (importantly the absence of the SRY gene sex determining region of the Y chromosome) once the ovaries form, there is a lack of production of both androgens (T and DHT) and antimullerian hormone AMH. The absence of the hormones cause the regression of the wolffian ducts and male genitals dont form, the mullerian ducts develop into the female reproductive tract

Question 2

Stages of follicular growth

Answer 2

The ovum matures (one each menstrual cycle) in a follicle composed of fluid and steroidogenic cells, once the ovum is ovulated, the cells that remain behind form the corpus luteum (rich in steroids), if pregnancy does not happen, corpus luteum dies and another cycle starts

Question 3

Oogenia throughout life

Answer 3

The number of oogonia in the fetal ovary peaks at 77 mill at 6 months of fetal development, OOgonia starts to degenerate via atresia that continues until meno (usually at birth 2 million left)

Question 4

Pattern of hormones and oogonia from conception until the end of puberty (menstrual cycle becomes normal)

Answer 4

hCG from the placenta and FSH and LH stimulate oogonia in the ovaries,

then 2-6 moth of age, FSH and LH peak again

before first menstrual cycle (menarche) the pituitary secretes FSH and LH which induces ovarian function (production of estrogen)

Question 5

Ovarian and placental steroidogenisis

Answer 5

The pathways to DHEA and androstenedione is catalyzed by the same enzymes in the adrenal

Cholesterol makes Pregnenolone
1. Pregnenolone-> 17ahydroxy pregnenolone->DHEA-> androstenedione

2. Pregnenolone-> progesterone-> 17 a progesterone -> androstenedione-> testosterone

Androstenedione or Testosterone -> Estrone (E1) or Estradiol (E2) via AROMATASE (secreted from ovary)

Fetal adrenal/hepatic androgen-> estriol (E3) placental aromatase- usually only found in pregnant women

Question 6

Gonadal steroids and their binding to plasma proteins

Answer 6

SHBG (sex hormone binding globulin) CBG (cort binding globulin

Estrogen does bind to SHBG but it binds much more tightly to albumin
Progesterone looks like cortisol (binds a little to CBG

SHBG binds to T and DHT
albumin does bind to androstenedione

Question 7

Brain Puberty

Answer 7

Increased leptin (fat signals) stimulate hypothalamic pulsatile release of GnRH (through kisspeptin neurons)

Question 8

Kisspeptin function

Answer 8

Kisspeptin is a neuron in the hypothalamus that mediates the effects of leptin (and neg and pos feedback) of estrogen on GnRH

Leptin-> kisspeptin to stimulate GnRH-> FSH and LH -> gonadala steroids (estrogen)–I Kisspeptin

Question 9

Female puberty

Answer 9

GnRH pulses start at about 9 years old-> first increase of FSH and then LH, Restart ovarian follicular development and the production of estradiol

Estrogen -> increase in growth, secondary sex characteristics

Menstrual cycles is the last occurrence of puberty, estrogen induces the closure of the growth plates at thend of the growth spurt

Question 10

Menstrual Cycle

Answer 10

Day 1 is the first day of menstruation:

From day 1 to ovulation (day 14) (follicular phase) because the follicle is the dominant ovarian structure. From ovulation to the death of the corpus luteum (luteal phase)

1. no pregnancy (therefore no hCG) corps leuteum dies and progesterone and estrogen levels go down
2. loss of negative feedback from estrogen-> increase in FSH (with a little LH)
3. increase in FSH induces maturation of the next group of follicles
4. Dominant follicle forms (at 4 days) and begins to release estrogen by itself
5. The increase in estrogen lowers the levels of FSH and LH via negative feedback
6. The decrease in FSH leads to atresia (death) of the non dominant follicles
7. As the dominant follicle grows it produces more and more estrogen
8. when estrogen peaks, it induces a switch in the hypothalamus and pituitary (kisspeptin) and instead of negative feedback, there starts to be postivie feedback and estrogen stimulates an LH surge (and a little FSH)
9. The LH surge stimulates ovulation and the formation of the corpus luteum
10. corpus luteum makes a lot of progesterone and a little estrogen (to inhibit FSH and LH)

Question 11

Mechanism of the generation of the positive feedback induced LH surge

Answer 11

1. early in follicular phase (menses), dominant follicle produces estrogen that acts locally (autocrine and paracrine) to stimulate more FSH receptors on granulosa cells (allows the follicle to survive the decrease in FSH)
2. in the middle of the follicular phase, local estrogen positive feedback induces more FSH and LH receptors on granulosa cells (it also increases the amount of estrogens
3. As estrogen peaks in late follicular phase, local estrogen feedback has induced such a positive feedback that there are a large number of granulosa cells, and the large increase in estrogen in the blood leads to an increase in LH and FSH leading to the LH surge

Question 12

role of inhibin

Answer 12

inhibin is produced from the ovaries and inhibits FSH release (why FSH is lower in the surge)

Question 13

Interaction of follicular theca cell and granulosa cell on production of estrogen

Answer 13

The theca cells are stimulated by LH and LDL produce androgens that diffuse (cholesterol->pregnenolone->progesterone-> androgens)

Androgens diffuse into the granulosa cell. In mature follicles, FSH acts on granulosa cells stimulates aromatase activity to convert the androgenns to estrogens.

Question 14

Effects of estrogens and progesterone

Answer 14

Estrogen predominates in the follicular phase and progesterone predominates in the luteal phase

ovuducts: estrogen increases cilia and contraction, progesterone increases secretion and decreases contractility

Uterus: estrogen increases proliferation, growth, contractility and watery secretion. Progesterone increases differentiation and secretion, decreases contractility dense and viscous secretion

Question 15

Endometrial/ uterine cycle

Answer 15

Proliferative phase during follicular phase and is the growth of the endometrium stimulated by estogens

Secretory phase occurs during the luteal phase due to progesterone primarily from the corpus luteum.

Uterine spiral artery vasoconstriction is signaled by the decline of progesterone and estrogen at the end of the luteal phase, leading to sloughing of endometrium and menstrual bleed

Question 16

Rescue of the corpus luteum by hCG after implantation of the blastocyst in the endometrium

Answer 16

After ovulation fertilization occurs, blastocyst enters the uterus at 5 days after the LH peak. Implantation occurs after 7 days, then hCG is secreted from trophoblasts and rescues corpus luteum.

hCG stimulates progesterone and estrogen release and inhibits FSH and LH release preventing menstraul cycles during the first trimester and stimulates continued growth of the endometrium to nurture the fetus

Question 17

Steroidogenic pathway in the trophoplast

Answer 17

LDL (cholesterol) is is taken up by the trophoblast

cholesterol-> pregnenolone in mito

Pregnenolone-> fetal adrenals and processed into adrenal steroids

Pregnenolone-> converted to progesterone in the SER and progesterone is secreted into maternal secretion

Question 18

Placental steroidogenesis

Answer 18

The placenta expresses a lot of aromatase (converts androgens to estrogens)

1. Maternal adrenal testosterone is converted to estradiol in the trophoblast
2. fetal adrenal using progesterone from trophobalst synthesizes DHEA and then sulfates it (sulfatase)
3. DHEA from maternal adrenal and DHEAs from fetal adrenal are converted to estrone in the placenta
4. Fetal DHEAs is converted to 16 DHEAS in fetal liver and aromatized to estriol in the placenta (estriol is a good measure of fetal HPA axis, hepatic and placental health)

Question 19

Rates of secretion of estrogens and progesterones and concentration of HcG

Answer 19

HCG peaks in first trimester of pregnancy
placenta is responsible for most of E and P in second trimester, so corpus luteum is not needed and HCG wanes

Placental steroidogenisis uses maternal and fetal androgens

Question 20

hormones in pregnancy

Answer 20

ANT pituitary: GH and ACTH unchanged, LH and FSH decreased (due to estrogen and progesterone neg feedback). PRL (prolactin releasing lactinogen) increases steadily throughout gestation preparing breast for lactation. TSH (hCG increase leads to a decrease b/c similar to TSH, because TH is stimulated by hCG). thyroid hormone is needed for early fetal development. TSH is the same at the end of pregnancy as notmal (total T4 is elevated due to increase in TBG but fT4 is normal)

Placental proteins: Because hCG has homology with GH and hPL -> insulin resistance (to supply glucose to fetus). CRH at end of pregnancy is hypothesized to contribute to labor

Estogens all go up throughout
Androgens (Testosterone goes way up)

Question 21

Thyroid hormones throughout pregnancy

Answer 21

changes happen over months
Total hormone increases due to increases in binding hormones, but free T3 and T4 stay regulated (through pituitary thyrotrophs)

Question 22

CV and pulm system affected by pregnancy

Answer 22

HR: up, BP: down, Stroke volume: increases, output: up, venous distenstion: up, venous resistance: down

Pulm:

Res Rate: unchanged, tidal volume: up, reserve: down, r. min col: increases

Question 23

phases of partuition

Answer 23

Phase 1: progesterone mostly from placenta maintains quiescence

Phase 2: Estrogen increases (progesterone receptors decreases) uterine stretch activates gap junctions, increased prostaglandin synthesis and oxytocin receptors increase (POSTITIVE FEEDBACK)

Phase 3: local prostaglandins and oxytocin from the posterior pituitary stimulates uterine contraction (POSITIVE FEEDBACK)

Phase 4: post partum-decrease in uterine activity

Question 24

Oxytocin positive feedback

Answer 24

happens in phase 3
As fetus head pushes on cervix, afferent nerves carry impulses in hypothalamus so oxytocin is released from nerve endings on posterior pituitary. Oxytocin stimulates uterine contractions that increase cervical stretch and so on.

After delivery from the placenta, estrogen decreases dramatically, which releases the mammary glands to synthesize milk. Suckling stimulates nerve endings in the nipple, stimulates myoepithelial cells in the mammary glands to let down milk

Question 25

the breast

Answer 25

Myoepithelial cells respond to oxytocin and forces milk into the ducts

Prolactin stimulates lactogenisis from the milk secreting epithelial cells

Question 26

Changes in rate of Estrogens, progesterone, prolactin after birth

Answer 26

Prolactin decreases to basal levels after a few weeks post partum

Prolactin will increase after an hour of suckling

Prolactin will inhibit FSH and LH release (menstrual cycles are unlikely)

Question 27

Estrogen secretion throughout life

Answer 27

peaks at every luteal phase and decreases at menopause when the ovaries cant make mature follicles