Plasma cortisol and cortisone in pregnancies with normal and anencephalic fetuses.

Plasma cortisol (F), cortisone (E), and progesterone (P), were measured in the umbilical vein (UV), umiblical artery (UA), and maternal peripheral vein (MPV) of 17 normal patients, and of 8 patients carying anencephalic fetuses. The plasma F in MPV of patients undergoing vaginal delivery after labor of spontaneous onset was significantly higher than that of patients delivered by elective cesarean section, whereas the plasma F concentrations in the UA or UV of the 2 groups were not statistically different from each other. The anencephalic fetuses had UA plasma F and E concentrations which were significantly lower than those of normal fetuses, suggesting that a main portion of UA cortisol and cortisone originates in the fetal adrenal. The UV and MPV plasma F and E concentrations of patients carrying anencephalic fetuses did not differ, however, from those of normal patients, suggesting that these UV corticoids are derived mainly from maternal sources. The amniotic fluid cortisol levels of the patients carying anencephalic fetuses were lower than those observed in the normal pregnancies, suggesting that amniotic fluid cortisol is derived mainly from fetal sources.

Adrenal steroids in maternal and cord blood after dexamethasone administration at midterm.

We undertook a study designed to evaluate whether it is feasible to suppress fetal adrenal secretion of androgens at mid-pregnancy by giving dexamethasone (DX) to the mother. Levels of DX and adrenal steroids were measured in maternal and cord plasma of 13 DX-treated and 16 untreated mothers undergoing abortion at 18-20 weeks of pregnancy. Maternal adrenal suppression was evidenced by a sharp fall of plasma cortisol (F), cortisone (E), corticosterone (B), and dehydroepiandrosterone sulfate (DHEA-S). However, in cord blood no fall of DHEA-S or corticosterone sulfate (BS) was found up to 20 hours after DX administration, and cord plasma ACTH remained detectable. The failure of DX to suppress the fetal adrenal at mid-pregnancy suggests that this drug would not be effective in the intrauterine treatment of congenital adrenal hyperplasia (C.A.H.).

Comparison of human chorionic gonadotropin measurements by radioimmunoassay and in vitro bioassay.

A sensitive, accurate, and reproducible in vitro bioassay was developed for measuring human chorionic gonadotropin (hCG), based on testosterone production by collagenase-dispersed interstitial cells of rat testes in response to hCG. The results were compared to those obtained by established beta hCG radioimmunoassay. The assay sensitivity was 25 pg hCG-CR119/ml (65 microIU second IRP/ml). The intra-assay coefficient of variation (CV) was 8.8%, and the interassay CV was 13% and 33% in the high and low ranges of the standard curve, respectively. hCG recoveries were 89.6 +/- 3.12% (SE, n = 12). The pattern of serum bio-hCG followed established patterns of immuno-hCG, with the highest level measured during the first trimester (mean, 52,600 +/- 7,250 SE (mIU/ml, n = 11), decreasing thereafter to a mean value of 7,400 +/- 1,500 mIU/ml at term. The mean ratio of the bio/immunoactivity was consistently greater than one and did not significantly change at the various stages of pregnancy, or between normal and molar pregnancies (first trimester, 1.75 +/- 0.12 SE; midtrimester, 1.46 +/- 0.12; term, 1.50 +/- 0.09; molar, 1.55 +/- 0.2). When serum bioactive and immunoactive hCG were measured in a woman at five weeks of pregnancy, an episodic secretion of hCG was obtained by both assays.

Conversion of progesterone to corticosteroids by the midterm fetal adrenal and kidney.

Midterm fetal adrenal and kidney tissue homogenates were incubated with 3H-progesterone (1 microM) and its conversion to te 3H-corticosteroids metabolites studied. Cortisol (36.3%) and corticosterone (4.7%) were isolated from the adrenal, and 11-deoxycortisol (32.5%) and deoxycorticosterone (21.1%) from the kidney. The results of these incubations confirmed the presence of 17- and 21-hydroxylase activities in both fetal tissues, and that of 11 beta-hydroxylase activity only in fetal adrenal tissue. We conclude that during pregnancy when progesterone levels are high, biosynthesis by the fetal kidney of 11-deoxycortisol, the most abundant corticosteroid formed by this tissue in this investigation, might provide to the fetal adrenal an important precursor for cortisol biosynthesis within the fetal compartment.

Direct evidence of sudden rise in fetal corticoids late in human gestation.

Glucocorticoids accelerate fetal lung maturation in all mammals studied, and in some species, such as goat and sheep, concentrations of fetal cortisol increase sharply before term, bringing about a train of events leading to parturition. Studies of cortisol in the umbilical cord blood have revealed no such increase at the end of human pregnancy. But information obtained in that way is difficult to interpret because much of the fetal cortisol is of maternal origin and its concentration, if sampled at delivery, is affected by maternal stress. These problems can be avoided to some extent by studying other fetal corticoids. Corticosterone sulphate (once called compound B, and abbreviated to BS) is produced by fetal adrenal glands and is present in greater concentrations in human fetal plasma than in maternal plasma. It is hydrolysed by the placental sulphatases and is a poor substrate for for placental 11 beta- hydroxysteroid dehydrogenase. We report here confirmation that the bulk of maternal BS originates from the fetus, and that its concentration increases suddenly at term.

Estrone sulfatase activity in the human brain and estrone sulfate levels in the normal menstrual cycle.

When the plasma concentrations of estrone sulfate (E1S) were measured in five menstrual cycles, the highest concentrations were found on the day of LH peak (14.25 nmol/l +/- 2.94 [SE]). Peak levels of E1S were 20 times higher than the highest E2 levels measured (0.769 +/- 0.276 nmol/l). To determine whether E1S can be metabolized by adult and fetal tissues we examined estrone (E1) sulfatase activity in brain and other tissues. E1 Sulfatase activity was present in all tissues studied including adult endometrium, fat and skin. When the rate of sulfatase activity was measured in homogenates of fetal hypothalamus, frontal cortex and pituitary (n = 4), the hypothalamic activity (306.0 +/- 39.1 [SE] pmol/min/mg protein) was significantly higher than that of the frontal cortex (127.4 +/- 19.4, P less than 0.002) or pituitary (193.7 +/- 43.3, P less than 0.03). This was not apparent in the adult (n = 2) where the enzyme activity was similar in the hypothalamus (413.9 +/- 27.3) and frontal cortex (446.3 +/- 82.2) and lower in the pituitary (98.2 +/- 19.2). The Km for E1 sulfatase in the fetal frontal cortex was 28.9 microM. The high E1 sulfatase activity in estrogen responsive target tissues, particularly fetal hypothalamus, accompanied by a large circulating reservoir of E1S, suggest that this enzyme could possibly have a regulatory role in controlling the level of intracellular estrogens and in modulating their intracellular function.

Endurance training effects on plasma hormonal responsiveness and sex hormone excretion.

A prospective study of the hormonal effects of a moderate exercise training program (4-wk control, 8-wk training) was conducted in seven young women. Sixty-minutes continuous bicycle ergometer tests of fixed relative intensity were performed at the beginning, middle, and end of the training period. The capacity of these acute bouts of exercise to affect circulating levels of stress markers, reproductive hormones, and hormones with possible antireproductive potential was measured. In addition, the urinary excretion of reproductive hormones was monitored continuously via serial overnight urine collections. Within testing sessions, plasma concentrations of all stress markers and antireproductive hormones rose significantly. Across testing sessions, only beta-endorphin + beta-lipotropin and cortisol exhibited an increment in peak responses as training progressed. Plasma reproductive hormone levels showed insignificant acute changes, and cyclic menstruation and preovulatory gonadotropin surges continued in all subjects. However, ovarian function was disturbed in four subjects as evidenced by a decreased excretion of estriol, free progesterone, or both. Transient infertility is a known clinical accompaniment of hormonal changes of comparable subtlety.