W8L2-3 Female Reproductive System 1&2 Flashcards
The female gonads are the ____, which, together with the _____ and _____ constitute the female reproductive tract
Ovaries; uterus; fallopian tubes
Two functions of ovary:
- oogenesis, 2. secretion of female sex steroid hormones (progesterone and estrogen)
What is the normal range of days of the ovarian cycle?
When is the “start” of the cycle?
25-30 days (28 days by convention)
Starts at menstruation
What is the first half of the ovarian cycle called?
What is the midpoint?
What is the second half of the ovarian cycle?
1st 14 days = Follicular Phase
@14 days = Ovulation
2nd 14 days = Luteal Phase
Do females keep producing new oogonia after fetal development?
No, they start with around 2 million oocytes at birth, and by puberty 400,000 remain. By menopause, only a few are left.
What is the dominant hormone of the follicular phase?
What undergoes development during this period?
Estradiol, which is the most important estrogen in non-pregnant women.
The dominant follicle develops.
What is the dominant hormone of the luteal phase?
What undergoes development during this period?
Progesterone (P4) {also E2 but P4 is dominant}
Corpus luteum develops
What are the two phases of the endometrial and myometrial cycles?
- Proliferative phase: endometrium regenerates, myometrium is excitable during sex
- Secretory Phase: endometrium proliferates secretory glands and fills with fluid, myometrium excitability decreased
At the end of the ovarian cycle, [progesterone] decrease causes what two things to occur that ultimately lead to menstruation?
- Uterus secretes Prostaglandin F2α (PF2α) which causes vasoconstriction, leading to necrosis of outermost uterine layer, erosion of walls
- Progersterone decline induces apoptosis, causing matrix metalloprotease activity to increase, also causing erosion of vessel walls, causing bleeding
What are the effects of estrogens during puberty?
Development of external genitalia, myometrium, breasts, other secondary sex characteristics
What are the effects of estrogens on myometrium in adults?
Oxytocin receptors increase, making the myometrium more excitable
What is the name for E1, E2, E3?
E1: estrone
E2: estradiol
E3: estriol
How many carbons are in androgens vs estrogens?
Androgens are 19C, Estrogens are 18C
What are the effects of estrogens on cervical secretions?
More fluid, less viscous secretions, lubricating the vagina and having short carbon-chain fatty acids introduced to give scent
What is the difference between the effects of Progesterone vs Estrogens on the motility of fallopian tube and cilia?
Estrogens increase motility, Progesterone decreases it
What hormonal changes cause the “LH surge” to occur?
Normally E2 is at lower concentrations and inhibits LH/FSH secretion via negative feedback
LH surge occurs with high concentrations of E2, when different receptors are activated and cause increased LH/FSH secretion via positive feedback (only in females)
What is the effect of the LH surge?
Ovulation occurs at the appropriate time, and only the biggest follicle is able to mature while the others degenerate
During pregnancy, prolactin secretion increases but lactation does not occur. Why?
Prolactin stimulates breast alveoli development but lactation does not occur bc estrogen concentration is high
What are the effects of estrogens on bone?
Induces closure of epiphyseal cartilage
OPG increases, causing decreased osteoclast activity and mineral content to increase
Deficiency of estrogen (as in menopause) leads to osteoporosis
What is the effect of estrogens on blood pressure?
Estrogens induce activity of eNOS, causing NO to be produced and vasodilation occurs, lowering BP
What are the effects of estrogens on hepatic metabolism?
Synthesis of antiotensinogen and TBG (thyroxine binding globulin) increases, while antithrombin synthesis is decreases
May be problems with thyroid hormone level or goiter during pregnancy
What are the effects of estrogens on blood clotting?
Because of [antithrombin] decrease, risk of blood clots increases, especially in females with Leyden mutation taking oral contraceptives
What are the effects of estrogens and the likelihood of cancer?
Considered “mitogens” - promote breast and cervical cancer, also a risk of oral contraceptives
What are 3 ways that progesterone facilitates fertilization?
- facilitates uptake of spermatozoa in uterus
- chemotactic stimulus for sperm cells
- facilitates implantation and early embryonic development via secretory endometrium
What is “superfecundation?” How is it prevented?
When separate acts of sex are able to fertilize more than 1 ova (making fraternal twins, possibly with different fathers)
Inhibited by Progesterone causing the LH secretion to decrease after LH surge, leading to no new ovulation.
What are 3 ways that progesterone helps maintain gestation?
- Decreases excitability of myometrium (decreases effect of oxytocin)
- Inhibits maternal NK cells that might attack the fetus
- Promotes alveolar system development in breasts
What are some non-ovarian tissues that contain aromatase?
What is the effect of this enzyme?
Brain, adipose tissue, bone, vascular endothelium, smooth muscle
Converts 19C androgens to 18C estrogens. Females usually have more fat than males, but both get some estrogens this way
Note: be able to draw ovarian cycle graph
I can’t put images here. Slide 11 on powerpoint.
What happens to body temperature during the ovarian cycle?
It is slightly decreased in the follicular phase through day 17 or so, then increases in luteal phase
In females, cholesterol is converted to androgens in _______ cells, then converted into estradiol in ______ cells. Why?
Theca interna cells; Granulosa Cells
Granulosa cells cannot convert C21 steroids to androgens, and theca interna cells do not have aromatase
What pituitary hormone receptors do theca interna cells have? And granulosa cells?
Theca interna: LH receptors
Granulosa cells: FSH receptors
What type of G protein coupled receptor does LH have for theca interna cells? What is the effect?
Gs -> cAMP
Increases activity of cholesterol conversion to progesterone, leading to more/faster androgen production
What type of G protein coupled receptor does FSH have for granulosa cells? What are the effects?
Gs -> cAMP -> many effects
Increases synthesis of P4 from cholesterol (P4 can diffuse out but cannot become androgens)
Increased conversion of Androgens (from Theca Interna cells) to E2
Production of inhibin and cytokines
What are the important hormonal effects of androgens at about day 10 of the ovarian cycle?
Induces HDL uptake required for E2 synthesis and increases sensitivity to FSH.
Without these effects, the negative feedback of E2 would otherwise be too powerful for the ovarian cycle to function
What hormone increases on day 14 that is important for the rupture of the follicle and release of the oocyte?
17-OH Progesterone
What major hormone is released by the embryo if fertilization occurs? What happens to the corpus luteum?
hCG is released (by trophoblast cells about 1 week after fertilization)
Corpus luteum graviditatis survives for ~3 months, producing progesterone to maintain new pregnancy
Estradiol and P4 induces what sequence of events that leads to inhibition of GnRH via negative feedback?
Arcuate nucleus (hypothalamus) produces more POMC, which makes more beta endorphins, which inhibit GnRH production (aka the error signal)
What special peptide is produced in the hypothalamus and induces GnRH release?
What is the difference between its neurons having low affinity and high affinity E2 receptors?
Kisspeptin 54
High-affinity E2α receptors: bind to low [E2] to reduce Kisspeptin release and slow GnRH secretion (neg feedback)
Low-affinity E2β receptors: bind to high [E2] and induce Kisspeptin release (positive feedback with LH surge) - only exist in females!
What is the difference between the time between pulsatile secretions of GnRH during the follicular vs luteal phases?
Follicular has shorter gaps between secretions than Luteal, 1.5 hours (follicular) vs 5-6 hours (luteal)
What are some factors that can alter the FSH / LH ratio?
Emotion, Prolactin, Suckling of Baby, Progesterone, Melatonin
What are 3 ways that the CNS has effects on the production of sex steroids?
- Light (darkness leads to melatonin release, and without sporadic melatonin, there is no ovarian cycle)
- Smells (+ pheromones)
- Psychological effects (like getting married)
Note: Draw diagram of neg feedback from Slide 21
Yes
Oral contraceptives involve a combination of what 2 hormones? What is important about the timing?
Estrogens and Gestagens, and importantly the gestagens are delivered during the follicular phase to inhibit LH surge and thus preventing ovulation
(+gestagens also inhibit sperm motility and implantation)
What is used as an oral contraceptive as the “morning after pill?”
A large dose of estrogen to induce menstruation
What days of the ovarian cycle does fertilization usually take place? And where?
Between days 12-17
Usually occurs in the ampulla of the fallopian tube
What are 3 major functions of hCG?
- Maintains corpus luteum so that it can produce progesterone and prevent myometrial contraction while lowering maternal LH
- Serves as indicator for pregnancy
- Promotes testosterone production in male fetuses
How is it that E3 levels rise in the pregnant mother?
In fetal adrenal cortex, cholesterol is converted (multiple steps) to DHEAS. DHEAS goes to the fetal liver and is converted to 16-OH-DHEAS. This goes to the placenta and is converted to E3, which is the most important estrogen of pregnancy
(slide 28**)
What are 4 important roles of cortisol in fetal development?
- surfactant production
- intestinal villi
- glycogen deposits in liver
- closure of ductus arteriosus
What happens to the estrogen : progesterone ratio right before birth?
It increases, causing increase density of oxytocin receptors, making the uterus more sensitive to contractile stimuli
What is the positive feedback loop that occurs to help uterine contractions during birth?
CRH -> ACTH -> DHEA -> E3 / P4 ratio increase -> Prostaglandin F2α increase in myometrium and decidua -> myometrium contraction
-> stretch of cervix and vagina, mechanoreceptors stimulated -> oxytocin increase -> contraction of myometrium
(slide 31)
What event after birth makes prolactin effective in promoting breast milk production?
Delivery of placenta -> E3 decrease, which allows PRL to function to increase breast milk
How is PRL secretion increased? How is it decreased?
Increased by VIP and breastfeeding
Decreased by dopamine
