What happens to the female hypothalamus at puberty?
It becomes desensitized to the negative feedback gonadal steroids. LH surges begin. Also, the positive feedback of estrogen is established.
What factors are integrated by the hypothalamus that determine when it is the right time to ovulate?
Steroid messengers from ovary, nutrition, emotion and sleep-wake patterns.
When is gonadotropin secretion the lowest in the female? The highest?
Lowest in prepubertal phase. Highest in postmenopausal phase. Secretion is pulsatile during the fertile years.
Why are menstrual periods less frequent closer to puberty? Why are the less frequent closer to menopause?
Puberty: Erratic gonadal hormone secretions and immature hypothalamus. Menopause: gradual decline in negative feedback action of ovarian steroids.
What are the two phases of the menstrual cycle?
Follicular (early & late) and luteal phase.
What marks the transition of the follicular phase to the luteal phase?
What hormone is the dominant driver of the follicular phase?
Estrogen. Increased estrogen production by the granulosa cells causes uterine growth, cervical secretions that favor sperm, ovary sensitization to actions of LH/FSH and evokes ovulatory surge.
What hormone is the dominant driver of the follicular phase?
Progesterone from the corpus luteum. This quiets uterine contractions, cervical secretions no longer favor sperm and feedback inhibits FSH release.
How does estradiol synergize with FSH during the follicular phase?
FSH induces proliferation of granulosa cells, which produce the aromatase that converts androgen to estradiol. Estradiol also stimulates proliferation of granulosa cells and follicle development. During this time granulosa cells are also increasing expression of FSH and LH receptors.
What cells are the primary target of LH?
Theca cells. LH induces androgen synthesis in theca cells. Granulosa cells then turn this androgen into estradiol and diffuses into the general circulation.
What is the main sentinel for the hypothalamus that determines when ovulation occurs?
Estrogen levels progressively rise as the follicles continue to mature. Once the “critical profile” of estrogen is reached, the hypothalamus induces the LH/FSH surge that triggers ovulation.
What is the likely mechanism that estrogen sparks the hypothalamus to induce ovulation?
Estrogen can be converted to a catecholestrogen, which can mediate neuronal signaling in the hypothalamus.
When does the woman’s basal body temperature begin to rise in the menstrual cycle?
After the LH surge as progesterone levels begin to rise.
What is the mechanism by which the signal from the ovary is amplified to trigger maximum hypothalamic response when it is time to ovulate?
GnRH is released in a pulsatile nature such that with each successive pulse, pituitary gonadotropins LH and FSH are increasingly released.
How does estrogen act as a negative feedback signal to the hypothalamus?
In moment-to-monent control it is usually a negative feedback hormone. It is the profile of estrogen in the blood over the entire period of the follicular phase, rising on a daily basis, that acts as a positive feedback hormone to trigger LH/FSH surge.
What induces secretion of progesterone during the menstrual cycle?
LH surge causes ovulation and luteinization of the corpus luteum. LH influences the corpus luteum to release progesterone for about 14 days where it peters out if it is not fertilized.
What is the key event you should use as the starting point when considering the functional sequence of the menstrual cycle?
The serum rise in FSH that occurs 2 days prior to menstrual bleeding.
2 events that signal follicular ripening?
Accelerated secretion of estrogen from ovary and appearance of progesterone.
What happens in the luteal phase when implantation does not occur?
At about 14 days after ovulation, the corpus luteum regresses (luteolysis). Progesterone and estrogen levels decrease, leading to vasospasm a of the spiral arterioles and necrosis, desquamation and bleeding of the endometrium.
Where in the female reproductive tract does fertilization typically occur? How long does it take for the egg to actually implant after fertilized?
Fertilization occurs at the ampullary-isthmic junction. On days 2-3 the zygote is around the utter-tubal junction. On days 3-4 it enters the uterine cavity as a morula. On day 7 it implants as a blastocyst.
What serum proteins are responsible for carrying estrogen and testosterone? Cortisol and progesterone?
Estrogen and testosterone are carried by sex hormone binding globulins (SHBG). Cortisol and progesterone are carried by cortisol binding globulin (CBG). Serum albumin takes care of any spill over hormones. Note that estrogen is a very potent stimulator of SHBG and CBG production in the liver.
What is a good reflection of the levels of biologically active unbound hormone in circulation?
Urinary excretion of free hormone.
What is the principal site of steroid inactivation? What reactions take place here?
Liver. Glucuronidations increases water solubility for excretion. Reduction renders the hormones inactive.
What are the 3 functions of the cervix that relate to sperm?
Facilitation of rapid transport up uterine cavity, colonization of sperm in cervical crypts, slow release of sperm from cervical crypts.
What does the acrosome reaction that takes place in the female reproductive tract do for the sperm?
Allows it to interact with zona pellucida RECEPTORS and digest its way into the oocyte through the cumulus oophorus, corona radiata and vitelline membrane.
How does fertilization of the egg occur?
1) Sperm binds receptors on zona pellucida 2) Penetrates perivitelline membrane 3) Cortical granules are released to prevent polyspermy 4) Oocyte completes second meiotic division and forms another polar body 5) Male and female pronuclei fuse, form a mitotic spindle and cleave for the first time.
What cell types are present within the newly formed blastocyst?
Cytotrophoblasts: these are the outermost cells that will form the penetrating syncytiotrophoblast layer. Inner cell mass: gives rise to fetus and amniotic ectoderm. Hypoblast: gives rise to endodermal lining of yolk sac.
What are the major stages of implantation of the embryo?
1) Syncytiotrophoblasts begin to invade endometrium 2) Trophoblastic lacunae, yolk sac and amniotic cavity form and embryo is embedded in endometrium. 3) Primary villi form 4) Secondary villi form
Can implantation occur in the absence of progesterone?
What forms the placenta?
Fetal trophoblasts and the maternal decidua.
What are the main functions of the placenta?
1) Endocrine 2) Nutritional growth of developing fetus
Even in complete absence of maternal pituitary and ovarian function, a pregnancy can be maintained after the placenta is fully established. Why is this?
The trophoblastic tissue produces gonadotropins and steroid hormones that are adequate in themselves for maintaining gestation.
What placental hormone is secreted by the trophoblasts and what is its role?
hCG is secreted by the trophoblast and has a role similar to LH. Its major role is to maintain corpus luteum progesterone secretion, which tells the hypothalamus implantation has occurred. It is also key in stimulating testosterone secretion by the fetal testis. hCG has immunologic properties that prevent fetal allograft rejection and stimulates placental steroidogenesis.
What is the earliest definitive sign of pregnancy?
hCG appears in serum 1-2 days after implantation, peaks at 7-12 weeks and drops around week 14 where it remains constant. Note that hCG in urine can be assessed 18 days after ovulation.
What placental hormone is similar to prolactin and growth hormone?
Placental lactogen (hPL, chorionic GH or chorionic somatomammotropin). hPL is secreted primarily into maternal circulation and stimulates mobilization of maternal fat stores and ensures a constant supply of glucose to the fetus while sparing muscle (similar to GH). This is the hormone that can cause insulin resistance in the mother and gestational diabetes. hPL also promotes breast development and controls movement of ions across the amniotic membranes.
What placental protein has the highest concentration at term?
Why is progesterone feedback inhibition key after implantation?
It inhibits release of FSH/LH and thus prevents follicular maturation in a pregnant woman.
How does progesterone affect the uterus and breasts?
It maintains a rich vascular bed, maintains uterine and breast growth, decreases uterine motility in face of high estrogen levels, inhibits contractility and prostaglandin levels.
When does the placenta become the main source of progesterone?
How does estrogen affect the uterus and breasts?
It maintains uterine growth, promotes breast development, softens pelvic ligaments, increases carrier protein synthesis and produces clotting factors.
When does estrogen start coming from the placenta mainly?
What are the events that lead to pregnancy termination and parturition?
Progesterone decline -> Sustained high estrogen levels -> Prostaglandin formation (sensitizes myometrium for contraction) -> Up-regulation of oxytocin receptors -> Secretion of relaxin by corpus luteum and placenta (relaxes cervix and pelvic ligaments) -> Secretion of oxytocin by pars nervosa after uterus stretching from baby.
How is oxytocin a positive feedback loop?
Stretching of the uterus -> Oxytocin release -> Contraction of uterus -> Oxytocin release and on and on and on until the baby is gone and uterine stretching no longer occurs.
Mechanism of the estrogen-containing birth control pill
Hypothalamus fails to sense follicle ripening because estrogen increase is masked by birth control pill. No LH surge or ovulation occur.
Risk of taking a progesterone only birth control pill
High incidence of break through bleeding
Risk of taking an estrogen birth control pill?
Increased blood clotting = higher risk for adverse cardiovascular events
A patient presents with severe headaches, visual disturbances, abdominal pain, anxiety, nausea and dizziness. Labs reveal a + serum hCG and no toxins. What is likely causing her condition and how do you treat her?
Pre-eclampsia. Possible causes when toxins are ruled out include insufficient blood flow to fetus, maternal blood vessel injury, immune imbalance, poor diet and Mg/Ca deficiency. The only cure is delivery of the child. Her hypertension should be managed and corticosteroids can be given to improve liver/platelet function and promote fetal lung development for early delivery.
Hallmarks of pre-eclampsia
Hypertension and proteinuria