FIGURE 5-19 Plasma levels of progesterone, estradiol, estrone, estetrol, and estriol in women during the course of gestation. (Modified and redrawn with permission from Mesiano S: The endocrinology of human pregnancy and fetoplacental neuroendocrine development. In Strauss JF, Barbieri RL (eds) Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 6th ed. Philadephia, Saunders, 2009.) the principal urinary metabolite of progesterone. Before this time, however, corpus luteum removal will result in spontaneous abortion unless an exogenous progestin is given (Chap. 63, p. 1198). After approximately 8 weeks, the placenta assumes progesterone secretion, resulting in a gradual increase in maternal serum levels throughout pregnancy (Fig. 5-19). By term, these levels are 10 to 5000 times those found in nonpregnant women, depending on the stage of the ovarian cycle.
The daily production rate of progesterone in late, normal, singleton pregnancies approximates 250 mg. In mulrifetal pregnancies, the daily production rate may exceed 600 mg. Progesterone is synthesized from cholesterol in a two-step enzymatic reauiuI1. r.l�., L-l1UI:�L:lUl ;� C0il v'ci'tC. tv plcg.cidciC ';;ithi� the mitochondria, in a reaction catalyzed by cytochrome P450 cholesterol side-chain cleavage enzyme. Pregnenolone leaves the mitochondria and is converted to progesterone in the endoplasmic reticulum by 33-hydroxysteroid dehydrogenase. Progesterone is released immediately through a process of difusion.
Although the placenta produces a prodigious amount of progesterone, the syncytiotrophoblast has a limited capacity for cholesterol biosynthesis. Radiolabeled acetate is incorporated into cholesterol by placental tissue at a slow rate. he rate-limiting enzyme in cholesterol biosynthesis is 3-hydroxy3-methylglutaryl coenzyme A (HMG-CoA) reductase. Because of this, the placenta must rely on an exogenous source, that is, maternal cholesterol, for progesterone formation. he tro biosynthesis (Simpson, 1979, 1980). This mechanism difers from placental production of estrogens, which relies principally on fetal adrenal precursors.
Although there is a relationship between fetal well-being and placental estrogen production, this is not the case for placen tal progesterone. Thus, placental endocrine function, including the formation of protein hormones such as hCG and proges terone biosynthesis, may persist for weeks after fetal demise.
he metabolic clearance rate of progesterone in pregnant women is similar to that found in men and nonpregnant women. During pregnancy, the plasma concentration of 5a-dihydroprogesterone disproportionately rises due to syn progesterone and fetus-derived precursor (Dombroski, 1997).
hus, the concentration ratio of this progesterone metabolite to progesterone is elevated in pregnancy. The mechanisms for this are not deined completely. Progesterone also is converted to the potent mineralocorticoid deoxycorticosterone in preg nant women and in the fetus. The concentration of deoxy corticosterone is strikingly higher in both maternal and fetal compartments (see Table 5-1). The extraadrenal formation of most of its production in pregnancy (Casey, 1982a,b).