Birth in most animal species is triggered by the fetus through activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Preterm birth, may be associated with precocious activation of fetal HPA function, reflecting the fetal response to an adverse intrauterine environment. There is a progressive and concurrent increase of ACTH1-39 and cortisol (F) in the circulation of fetal sheep during the last 15-20 days of pregnancy (term, day 145-150) associated with increased expression of hypothalamic CRH pituitary POMC and adrenal ACTH receptor and steroidogenic enzymes, particularly P450 C17. Similar changes occur with fetal hypoxemia. Negative feedback is ameliorated by decreased pituitary and hypothalamic glucocorticoid receptor, increased CBG, and altered fetal pituitary 11B-hydroxysteroid dehydrogenase type 1. Repeated fetal hypoxemia, diminishes the fetal-pituitary ACTH response, but increases fetal adrenal responsiveness. Fetuses exposed to maternal glucocorticoid in late gestation are growth restricted with altered postnatal HPA responsiveness and glycemic responses that reproduce the insulin resistance of type 2 diabetes. We conclude that the level of fetal HPA activity is crucial not only for determining gestation length, but also predicts pathophysiologic adjustment in later life.

Summary A test of placental function was assessed by measurement of plasma oestradiol levels in 32 patients after intravenous injection of 50 mg dehydroepiandrosterone sulphate (DHAS). Every pregnant patient showed a rise in plasma oestradiol after DHAS; two puerperal patients showed no rise. It was not possible to distinguish the variable response in normal pregnancy from that in patients with severe hypertension and proteinuria or with retarded intrauterine fetal growth. The test was of no value in one hypertensive patient as a predictor of fetal death eight da ys later or, in another, to confirm fetal death of two days duration. Our results do not suggest that this test is a useful addition to currently available tests of placental endocrine function.

Serial measurements were made of the concentration of plasma unconjugated oestetrol in normal human pregnancy. The mean curve and limits of normal variation have been established. Plasma levels rose from just below 2 ng/ml at 20 weeks to approximately 5 ng/ml at term.

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