FIGURE 4-18 Serial increases in serum cortisol (blue line) and adrenocorticotropic hormone (ACTH) (red line) across normal pregnancy. (Data from Carr, 1981o.) apparent paradox is not understood completely. Some suggest that greater free cortisol levels in pregnancy result from a "resetting" of the maternal feedback mechanism to higher thresholds (Nolten, 1981). his might result from tissue reractoriness to cortisol. Others assert that these incongruities stem from an antagonistic action of progesterone on mineralocorticoids (Keller-Wood, 2001). Thus, in response to elevated progesterone levels during pregnancy, an elevated free cortisol is needed to maintain homeostasis. Other theories include possible roles for higher free cortisol in preparation for the stress of pregnancy, delivery, and lactation. This pattern might also influence postpartum behavior and parenting roles (Conde, 2014).
As early as 15 weeks' gestation, the maternal adrenal glands secrete considerably increased amounts of aldosterone, the principal mineralocorticoid. By the third trimester, approximately 1 mg/d is released. If sodium intake is restricted, aldosterone secretion is even further elevated (Watanabe, 1963). Concurrently, levels of renin and angiotensin II substrate normally rise, especially during the latter half of pregnancy. his scenario promotes greater plasma levels of angiotensin II, which acts on the zona glomerulosa of the maternal adrenal glands and accounts for the markedly elevated aldosterone secretion. Some suggest the increased aldosterone secretion during normal pregnancy afords protection against the natriuretic efect of progesterone and atrial natriuretic peptide. Gennari-Moser and colleagues (2011) provide evidence that aldosterone, as well as cortisol, may modulate trophoblast growth and placental size.
Maternal plasma levels of this potent mineralocorticosteroid progressively increase during pregnancy. Indeed, plasma levels of deoxycorticosterone rise to near 1500 pg/mL by term, a more than 15-fold increase (Parker, 1980). his marked elevation does not derive from adrenal secretion but instead represents augmented kidney production resulting from estrogen stimulation. The levels of deoxycorticosterone and its sulfate in fetal blood are appreciably higher than those in maternal blood, which suggests transfer of fetal deoxycorticosterone into the maternal compartment.
In balance, androgenic aCtiVlty rises during pregnancy, and both maternal plasma levels of androstenedione and testosterone are increased. This inding is not totally explained by alterations in their metabolic clearance. Both androgens are converted to estradiol in the placenta, which increases their clearance rates. Conversely, greater plasma sex hormone-binding globulin levels in gravidas retard testosterone clearance. Thus, the production rates of maternal testosterone and androstenedione during human pregnancy are increased. he source of this higher C19-steroid production is unknown, but it likely originates in the ovary. Interestingly, little or no testosterone in maternal plasma enters the fetal circulation as testosterone. Even when massive testosterone levels are found in the circulation of pregnant women, as with androgen-secreting tumors, testosterone concentrations in umbilical cord blood are likely to be undetectable. his results from the near complete trophoblastic conversion of testosterone to 173-estradiol.
Maternal serum and urine levels of dehydroepiandrosterone suate are lower during normal pregnancy. his stems from a greater metabolic clearance through extensive maternal hepatic 16.-hydroxylation and placental conversion to estrogen (Chap. 5, p. 103).