Endocrinology of Pregnancy
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How are LH and hCG similar and different?
- They share a common alpha subunit and the beta subunit is similar to LH with minor amino acid and charb diff.
- hCG has a longer c terminal tail with which it makes a longer half life
- hCG binds to the same receptor as LH and elicits the same biological responses
What is the HCG produced by and what is the primary function?
- hCG is produced by the developing blastocysts
- primary function is to rescue the corpus luteum and maintain luteal progesterone production. it ensures that the progesterone levels do not fall at luteolysus and the endometrium is maintained to support the implanting embryo.
How do the levels of hCG vary in the pregnancy?
levels rise during the first trimester and then decline
How is GnRH released? what is its function in the pregnancy?
it is normally released by the hypothalamus but during pregnancy it is also released by the cytotrophoblasts cells of the developing placenta to stimulate the production of hCG form the syncitiotrophoblasts
What is the function of HPL and where is it released from?
HPL is a protein hormone produced by the placenta and is a metabolic regulator which alters fuel availability by antagonizing maternal glucose and enhancing fat mobilization
What is HPL structured like?
It is structurally related to prolactin and growth hormone
What is the most important hormone of pregnancy and why is it essential?
- Progesteroneis essential for the establishment and maintenance of pregnancy.
- Progesterone maintains the endometrial or decidual lining of the uterus and it stimulates the glandula secretion of nutrients to support the implanting blastocyst.
- In addition P suppresses the maternal immunologic response to the fetal antigens present in the uterus thereby avoiding rejection of the implanting blastocyst.
- Finally, progesterone also maintains quiescence of the myometrium thus avoiding premature contractions that could disrupt pregnancy
How is progesterone secreted during pregnancy?
Progesterone is initially secreted by the corpus luteum in response to hCG produced by the developing blastocyst. At approximately 7-10 weeks of gestation, the placenta takes over progesterone production for the remainder of the pregnancy, and the corpus luteum slowly regresses.
Why is estrogen important in pregnancy?
- causes endometrial proliferation during the follicular phase of the menstrual cycle so there is an adequate lining for implantation.
- without estrogen priming during the follicular phase, progesterone alone cannot support pregnancy.
- Estrogen is also important during pregnancy to prepare the breast for lactation by stimulating branching and development of the alveolar ducts.
- Estrogen tends to have an opposite effect on the myometrium and stimulates uterine contractions, although the net effect during pregnancy is the dominance of progesterone to maintain uterine quiescence.
How is estrogen secreted throughout pregnancy?
- The source of estrogen also shifts from the corpus luteum to the placenta around weeks 7-10 of gestation however the production of certain estrogens, primarily estriol, require maternal-placental-fetal cooperation to accomplish steroidogenesis
- In order for estriol production to occur, the maternal endocrine system must work in concert with the placenta and the fetus.
How is estriol made in a pregnant woman?
- 1. Since the placenta cannot synthesize cholesterol on its own, it utilizes maternal cholesterol as the substrate for steroidogenesis (Figure 5).
- 2. The placenta converts cholesterol into pregnenolone and progesterone, but because it lacks CYP17 it cannot continue to process Pregnenolone or P into androgen or eventually estrogen. So in order to make these steroids the placenta uses substrates provided by the fetus.
- 3. Although the fetus lacks 3BHSD so it doesn’t make much in the way of progesterone itself, the fetal adrenal does contain a sulfotransferase so it can produce pregnenolone sulfate and DHEAS.
- 4. Importantly the fetal liver also contains an active 16 hydroxylase enzyme complex . This enzyme is found almost exclusively in the fetal liver, and adds a hydroxyl group to the steroid at position 16; using DHEAS as an example, will produce 16 OH DHEAS.
- 5. The placenta contains an active aromatase enzyme system so it will aromatize the 16-OH DHEAS into 16-hydroxy estradiol with is estriol.
- As such, the only way that estriol is present in the maternal circulation during pregnancy is if the maternal circulation provides cholesterol, the placenta converts it into pregnenolone, the fetus converts it into androgens and the 16 hydroxylates them, and the placenta then aromatizes the 16-hydroxylated androgens into estriol.
What is prolactins primary function?
Prolactin’s primary function is to prepare the breast for lactation, and the action of prolactin on lactation is inhibited by the high levels of placental steroids in the circulation
When is the inhibition to prolactin removed?
When E and P levels fall after parturition, the inhibition of Prl is removed and lactation can commence
What is the function of relaxin and from where is it released?
Relaxin is a protein produced by the CL and placenta and is responsible for relaxing the pelvic bones and ligaments in preparation for parturition. Along with estrogen it softens the cervix and in concert with P it inhibits myometrial contractions
What are the hormones that are used as markers of fetal well being during pregnancy?
- Alpha-fetoprotein is a glycoprotein hormone produced by the fetal liver which enters the maternal circulation. It is the most abundant circulating protein in the fetus and is sometimes considered to be the fetal form of albumin. AFP may be elevated in certain congenital malformations such as neural tube defects and may be decreased in certain trisomies such as Down syndrome
- Estriol is a pregnancy specific estrogen whose synthesis requires the coordination of the maternal, placental, and fetal endocrine systems. We will examine the synthesis of estriol in the next slide but low levels of maternal estriol levels can indicate certain fetal anomalies such as trisomy 18 and trisomy 21
- inhibin-a is sometimes also used as a marker of normal fetal development. During the menstrual cycle inhibin a is produced by the corpus luteum, but as with e and p, the placenta assumes production during pregnancy. Elevated levels of inhibin a are often found in Down syndrome and Turner syndrome, whereas inhibin a may be decreased in trisomy 18.
Triple Screen test
combination of hCG, AFP, and estriol
quad screen test
combination of hCG, AFP, inhibin-a and estriol
How does diabetes affect the woman and how does it happen during pregnancy?
During pregnancy, there are high circulating levels of several hormones that are antagonistic to insulin action including hPL, GH, and Prl. These can result in maternal insulin resistance, which results in decreased maternal glucose utilization. If maternal glucose uptake is reduced, circulating glucose levels can increase, and glucose readily crosses the placenta into the fetal circulation. In the fetus, the elevated glucose stimulates the fetal pancreas to produce insulin, and insulin levels are elevated in the fetal circulation. In the fetus, insulin is an important growth factor but cannot control glucose levels partly because of the continuous supply of elevated glucose from the maternal circulation. In uncontrolled gestational diabetes, infants are often larger for their gestational age than in unaffected individual
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