Female Flashcards
Genetic Sex is determined at conception
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
Stages of follicular growth
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
Oogenia throughout life
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)
Pattern of hormones and oogonia from conception until the end of puberty (menstrual cycle becomes normal)
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)
Ovarian and placental steroidogenisis
The pathways to DHEA and androstenedione is catalyzed by the same enzymes in the adrenal
Cholesterol makes Pregnenolone
1. Pregnenolone-> 17ahydroxy pregnenolone->DHEA-> androstenedione
- 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
Gonadal steroids and their binding to plasma proteins
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
Brain Puberty
Increased leptin (fat signals) stimulate hypothalamic pulsatile release of GnRH (through kisspeptin neurons)
Kisspeptin function
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
Female puberty
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
Menstrual Cycle
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)
- no pregnancy (therefore no hCG) corps leuteum dies and progesterone and estrogen levels go down
- loss of negative feedback from estrogen-> increase in FSH (with a little LH)
- increase in FSH induces maturation of the next group of follicles
- Dominant follicle forms (at 4 days) and begins to release estrogen by itself
- The increase in estrogen lowers the levels of FSH and LH via negative feedback
- The decrease in FSH leads to atresia (death) of the non dominant follicles
- As the dominant follicle grows it produces more and more estrogen
- 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)
- The LH surge stimulates ovulation and the formation of the corpus luteum
- corpus luteum makes a lot of progesterone and a little estrogen (to inhibit FSH and LH)
Mechanism of the generation of the positive feedback induced LH surge
- 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)
- 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
- 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
role of inhibin
inhibin is produced from the ovaries and inhibits FSH release (why FSH is lower in the surge)
Interaction of follicular theca cell and granulosa cell on production of estrogen
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.
Effects of estrogens and progesterone
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
Endometrial/ uterine cycle
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
Rescue of the corpus luteum by hCG after implantation of the blastocyst in the endometrium
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
Steroidogenic pathway in the trophoplast
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
Placental steroidogenesis
The placenta expresses a lot of aromatase (converts androgens to estrogens)
- Maternal adrenal testosterone is converted to estradiol in the trophoblast
- fetal adrenal using progesterone from trophobalst synthesizes DHEA and then sulfates it (sulfatase)
- DHEA from maternal adrenal and DHEAs from fetal adrenal are converted to estrone in the placenta
- 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)
Rates of secretion of estrogens and progesterones and concentration of HcG
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
hormones in pregnancy
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)
Thyroid hormones throughout pregnancy
changes happen over months
Total hormone increases due to increases in binding hormones, but free T3 and T4 stay regulated (through pituitary thyrotrophs)
CV and pulm system affected by pregnancy
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
phases of partuition
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
Oxytocin positive feedback
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
the breast
Myoepithelial cells respond to oxytocin and forces milk into the ducts
Prolactin stimulates lactogenisis from the milk secreting epithelial cells
Changes in rate of Estrogens, progesterone, prolactin after birth
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)
Estrogen secretion throughout life
peaks at every luteal phase and decreases at menopause when the ovaries cant make mature follicles
