Placental corticotropin-releasing hormone and pituitary-adrenal function during pregnancy

Abstract

The placenta secretes large amounts of the hypothalamic releasing hormone, corticotropin-releasing hormone (CRH), into both the maternal and fetal circulation during pregnancy. We characterized the relationship between maternal plasma CRH and products of the pituitary and adrenal in order to investigate the physiologic role of placental CRH in modulating maternal pituitary-adrenal function. Plasma was obtained from 8 women at biweekly intervals between 21 and 40 weeks of full-term pregnancy for CRH, adrenocorticotropin (ACTH), α-melanocyte-stimulating hormone (α MSH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) measurements by radio-immunoassay. Eighteen women were also studied once at 22-34 weeks of pregnancy with plasma CRH and 24-hour urinary free cortisol measurement. Eight nonpregnant women served as control subjects. Plasma CRH was undetectable in the nonpregnant subjects and rose over the time period studied in the pregnant women. Concentrations of afternoon ACTH and cortisol also rose during pregnancy while DHEAS levels declined in the pregnant women. The α-MSH levels were beneath the level of detection (<20 pg/ml) in both the pregnant and nonpregnant subjects. The overall mean afternoon ACTH concentration was higher in the pregnant than in the nonpregnant women (11.4 ± 1.8 vs. 5.9 ± 1.8 pg/ml; p < 0.05), although the ACTH levels in both groups remained within the normal range. The mean plasma cortisol concentrations were higher in the pregnant women, while the mean DHEAS levels were lower in the pregnant women when compared to the nonpregnant subjects. The urinary free cortisol concentration was also significantly higher in the pregnant than in the nonpregnant women (89.2 ± 14.5 vs. 29 ± 1 µg/ day; p < 0.05). The maternal plasma CRH concentration was significantly correlated with the 24-hour urinary free cortisol level (r = 0.71; p < 0.001). Thus we show that maternal plasma CRH, ACTH, cortisol, and urinary free cortisol rise during pregnancy, while plasma DHEAS declines. The present data strongly support the hypothesis that placental CRH is a physiologic regulator of the pituitary-adrenal axis and that these alterations of pituitary-adrenal function during pregnancy may be due in part to chronic placental CRH secretion.