Longitudinal Study of Progestins, Mineralocorticoids, and Glucocorticoids throughout Human Pregnancy*

Abstract

The maternal adrenal cortex seems to be involved in the adaptation to pregnancy. To study in detail adrenocortical secretion during pregnancy, we measured plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone simultaneously by RIA after extraction and automated Sephadex LH-20 chromatography of 10 normal pregnant women longitudinally throughout pregnancy at weeks 8-10, 14-17, 21-24, 28-32, and 38 as well as at the time of admission to the delivery room. The mean plasma progesterone and 17-hydroxy-progesterone concentrations increased from 37.2 +/- 6.5 (+/- SE) and 8.2 +/- 1.0 nmol/L, respectively, in early gestation to maximum levels of 138.0 +/- 25.7 and 22.8 +/- 2.2 nmol/L at week 38 (P less than 0.01). Plasma glucocorticoid levels rose 2- to 3-fold (P less than 0.01) from weeks 8-10 (corticosterone, 18.5 +/- 5.4; 11-deoxycortisol, 1.9 +/- 0.2; cortisone, 24.2 +/- 4.2; cortisol, 195.5 +/- 37.6 nmol/L) to week 38 (corticosterone, 42.9 +/- 11.2; 11-deoxycortisol, 4.6 +/- 0.5; cortisone, 71.5 +/- 13.6; cortisol, 420 +/- 63 nmol/L). Similarly, plasma mineralocorticoid levels increased 5- to 7-fold (P less than 0.01) from weeks 8-10 (11-deoxycorticosterone, 0.69 +/- 0.12; aldosterone, 0.41 +/- 0.08 nmol/L) to maximum levels at week 38 (5.3 +/- 0.9 and 2.1 +/- 0.3 nmol/L, respectively). At the time of admission to the delivery room, plasma 11-deoxycortisol, corticosterone, and cortisol concentrations were higher (P less than 0.02) than at 38 weeks, but plasma progestin and mineralocorticoid concentrations were not. We conclude that the source of the elevated maternal corticosteroid levels in pregnancy in addition to the estrogen-mediated rise in corticosteroid-binding globulin is the maternal adrenal cortex itself. The peak glucocorticoid levels at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor.

Gestational Age-Dependent Changes in Gene Expression of Metabolic Enzymes and Transporters in Pregnant Mice

“…CYP17A1 is a critical enzyme for steroid hormone biosynthesis. The large induction of hepatic Cyp17a1 (approximately 3-to 10-fold) suggests that production of 17a-hydroxyprogesterone and 17a-hydroxypregnenolone may increase during mouse pregnancy, which is consistent with 17a-OH progesterone increases in humans during pregnancy (Dörr et al, 1989). Increased levels of 17a-OH metabolites could ultimately increase estrogen production in the maternal liver; however, downregulation of placental Cyp17a1 throughout gestation favors progesterone formation, not estrogen.…”

Expression and Regulation of Glucocorticoid Receptor in Human Placental Villous Fibroblasts

“…In addition, 100 nm was the dose of DEX previously used to demonstrate GC-mediated down-regulation of GR (31,33,34,42). The observation that levels of cortisol in maternal sera range from approximately 200 -400 nm between 8 wk of pregnancy and term indicates that periplacental levels of GC are high throughout gestation (48).…”

Differential Modulation of TLR3- and TLR4-Mediated Dendritic Cell Maturation and Function by Progesterone

“…The microenvironment created during pregnancy differs from the normal physiological situation, particularly with regard to circulating hormones, and levels of glucocorticoids, estrogen, and progesterone are all increased. This change in the hormonal milieu is thought to play a major role in skewing the maternal immune response to a Th2 and T regulatory phenotype (12,13), influenced in part by actions of hormones on a number of hematopoietic cells including DCs (14,15).…”