CRH is synthesized in the hypothalamus and released in response to stress into the portal hypophyseal blood; an additional site of synthesis, the placenta, is present only during pregnancy. Placental CRH is released into the maternal and fetal circulation during human pregnancy, and we hypothesized that the chronic fetal stress associated with fetal growth retardation may stimulate placental CRH release. We measured plasma CRH concentrations in the umbilical cord blood of 28 growth-retarded fetuses and 28 normally grown fetuses matched for gestational age and mode of delivery. Plasma ACTH, dehydroepiandrosterone sulfate (DHEAS), and cortisol were also measured in the umbilical cord samples to determine if CRH levels were correlated with levels of pituitary and adrenal hormones. The mean umbilical cord plasma CRH level in the growth-retarded fetuses was 206 +/- 25.8 pmol/L, which was significantly higher than that in the normally grown fetuses matched for gestational age, presence or absence of labor, and mode of delivery (49.4 +/- 16.7 pmol/L; P < 0.01). The mean plasma ACTH level in the growth-retarded fetuses (5.7 +/- 1.2 pmol/L) was significantly higher than that in the normally grown fetuses (3.3 +/- 0.7 pmol/L; P < 0.05). The mean cortisol concentration in the growth-retarded fetuses was 260 +/- 32.5 nmol/L, and that in the normally grown fetuses was 220 +/- 40 nmol/L. The mean DHEAS level was significantly lower in the growth-retarded fetuses (4.8 +/- 0.6 mumol/L) than that in the normally grown fetuses (7.7 +/- 0.6 mumol/L; P < 0.001). There was a significant correlation between umbilical cord plasma CRH and both ACTH and cortisol concentrations as well as a significant negative correlation between CRH and DHEAS levels in the growth-retarded fetuses. The umbilical cord plasma CRH level is extremely elevated in growth-retarded fetuses compared to that in normal fetuses. Placental CRH, like hypothalamic CRH, may be stimulated in conditions of chronic stress and may modulate fetal pituitary-adrenal function in high risk pregnancies.

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The effect of pre-eclampsia on concentrations of corticotrophin releasing hormone (CRH) in umbilical-cord blood of fetuses at delivery was studied in order to determine if fetal CRH is elevated in this disorder when compared with uncomplicated pregnancy. Placental CRH may be a regulator of fetal pituitary-adrenal function and we therefore also measured ACTH, cortisol and dehydroepiandrosterone sulfate (DHEAS) in the umbilical-cord blood. The mean umbilical-cord plasma CRH in the fetuses from pregnancies complicated by pre-eclampsia, 667 +/- 153 pg mL-1, was significantly higher than the plasma CRH in the fetuses from normotensive pregnancies, 185 +/- 22 pg mL-1 (P < 0.001). The mean fetal cortisol concentration was significantly higher in pre-eclampsia, than in the normotensive, pregnancies (pre-eclampsia, 13.5 +/- 1.8; normotensive, 7.6 +/- 1.3 micrograms dL-1; P < 0.001). Plasma DHEAS was 217 +/- 23 micrograms dL-1 in the umbilical-cord blood of the fetuses from pregnancies complicated by pre-eclampsia and 281 +/- 35 micrograms dL-1 in the normotensive pregnancies (P < 0.01). Placental CRH synthesis and release, in contrast to hypothalamic CRH, appears to be stimulated by glucocorticoids. In pregnancies complicated by uteroplacental insufficiency, as may occur in pre-eclampsia, placental CRH production may be enhanced by increased fetal glucocorticoids. In turn, placental CRH may modulate fetal pituitary-adrenal steroidogenesis to favour increased cortisol secretion. Thus, placental CRH may play an important role in the fetal response to a compromised intrauterine environment.

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