AN INTRODUCTION TO PREGNANCY

AN INTRODUCTION TO PREGNANCY!

Maternal Recognition of Pregnancy

In the event that pregnancy is achieved, progesterone production by the corpus luteum is maintained and the endometrial mucosal layer continues to increase in thickness. How does the female know that she is pregnant? There must be some signal to maintain the corpus luteum and prolong progesterone production. Progesterone is essential to maintain pregnancy. Three of the important initial products of the corpus luteum of pregnancy (the corpus luteum verum) are progesterone, 17a-OH-progesterone and b-estradiol. It has been suggested that the human embryo is an aggressive, enzymatic, burrowing embryo. Following extensive migration through the uterus, the embryo implants and begins secreting hCG almost immediately, which provides a gonadotropic stimulus to salvage the corpus luteum. Again, note that LH and hCG act at the same specific membrane-bound protein receptors, the LH/hCG receptor. Thus, a gonadotropic stimulus from the implanting conceptus may salvage the corpus luteum. Nonetheless, the first major maternal endocrine event associated with pregnancy is maintenance of elevated progesterone levels. hCG production may be most important during the first trimester of pregnancy, to support progesterone production by the corpus luteum. By the second trimester, the placental syncytiotrophoblast of the chorionic villi will produce enough progesterone to maintain pregnancy.

Embryo

Periods of Gestation

i) The Period of the Oocyte

During the "period of the oocyte," fertilization has taken place, but maternal circulating endocrine profiles are not different than during the normal luteal phase. Implantation occurs about 6-7 days after fertilization, when the conceptus is a blastocyst of 1000-10000 cells. Trophoblast cells invade the endometrium and begin secreting hCG, which becomes detectable within approximately 24 hours of implantation, or 3 weeks of gestational age. "Gestational age" is normally calculated from the first day of the last menses preceding pregnancy. With a circulating half life exceeding 24 hours, maternal circulating hCG levels rise quickly. The most reliable chemical indicator of pregnancy in humans is hCG, specifically the unique beta subunit of the hCG molecule (hCG is a glycoprotein with alpha and beta subunits).

ii) The Period of the Embryo

The period of the oocyte really ends with maternal recognition of pregnancy and a change in the endocrine profile from that normally seen during the menstrual cycle. In humans this is associated with implantation and a continued rise of progesterone levels above those normally seen during the luteal phase.

iii) The Period of the Fetus

The period of the fetus is really thought to begin with implantation of the embryo. In humans, the aggressive embryo implants early, such that the "period of the oocyte" and the "period of the embryo" are brief. For a small review of fetal reproductive endocrinology, see gonadal and genital differentiation and puberty, above.

Endocrinology of the Placenta

chorionic somatomammotropin (hCS) or placental lactogen (hPL)

Aside from hCG production, which peaks late in the first trimester or early in the second trimester, the placenta produces a wide variety of proteins, including chorionic somatomammotropin (hCS, also known as placental lactogen, hPL), virtually all hypothalamic releasing factors, TSH-like and ACTH-like molecules, the "gonadal peptides" activin and inhibin, several cytokines (notably the interleukins) and numerous other proteins. Most "releasing factors" are synthesized by cytotrophoblast cells, while trophic factors are released by syncytiotrophoblast cells. Thus, the relationship between cytotrophoblast and syncytiotrophoblast cells has been likened to the relationship between the hypothalamus and anterior pituitary cells. hPL, rather than GH, is recognized as the "fetal growth hormone."

placental steroids

The syncytiotrophoblast are also recognized for their capacity to synthesize steroids, notably progestagens and estrogens. However, the syncytiotrophoblast cannot synthesize steroids de novo, and require precursors from maternal circulation. Placental progesterone secretion rises throughout pregnancy. After 7 weeks of pregnancy, the placenta can secrete sufficient progesterone to maintain pregnancy independently of the maternal pituitary and corpus luteum.

Substrates for placental estrogen production are supplied by the mother and the fetus but are primarily fetal adrenal androgens (specifically dehydroepiandrosterone sulfate or DHEAS). Placental sulfatase cleaves the sulfate group and uses DHEA to synthesize androgens, which the placenta can then aromatize to estrogens. Prolonged elevation of estrogens during pregnancy causes the maternal pituitary to undergo hypertrophy, particularly the lactotropes of the anterior pituitary. Maternal PRL levels rise continuously after the first trimester.

Endocrine changes imposed on the mother by the fetus

The fetus imposes demands on other maternal endocrine organs. Notably, maternal parathyroid activity is increased in response to a Ca²⁺ demand by the developing fetal skeletal system. Maternal thyroid activity must increase with the increase in renal iodide clearance. Maternal b-cell hyperplasia and hyperinsulinemia are associated with the development of peripheral insulin resistance following the first trimester of pregnancy. Maternal glucocorticoids (cortisol) double during pregnancy as a result of maintained estrogenic stimulation of cortisol binding globulin production by the liver. Elevated estrogen levels increase aldosterone production by the adrenal cortex, angiotensinogen production by the liver and renin production by the juxtaglomerular cells of the kidney. Increases in ovarian androgen production are counteracted by SHBG binding of testosterone and conversion of DHEAS to estrogens by the placenta. If you are unfamiliar with some of the hormones above, relax, most of them will become familiar in the Endocrinology section.