Aromatization of 15 alpha and 16 alpha hydroxylated androgens in the human placental using [1,2-3H]-substrates.

This in vitro study reports data on the aromatization of [1,2-3H]-C19 steroids in the human term placenta [androstenedione (III), testosterone (IV), 15 alpha-hydroxy-androstenedione (V), 15 alpha-hydroxy-testosterone (VI), 16 alpha-hydroxy-androstenedione (VII)]. The hydroxylated androgens were microbiologically synthesized from commercially radiolabelled [1,2-3H]-androstenedione and testosterone. Androstenedione and testosterone were good substrates for the human placental aromatase (low Km values, high Vmax); they strongly inhibited the 15 and 16 hydroxylated androgens aromatizations. On the other hand, these hydroxylated compounds acted as poor substrates and were only non-competitive inhibitors of the androstenedione and testosterone aromatizations. However, 15 alpha-hydroxy-androstenedione could not be disregarded as a potential precursor of 15 alpha-hydroxylated estrogens in the human placenta.

Estradiol and estetrol plasma levels before and after intravenous administration of dehydroepiandrosterone sulfate in normal and pathologic pregnancies.

Intravenous injections of 50 mg dehydroepiandrosterone sulfate (DHEAS) were given to 7 women with normal pregnancies and 5 with pathologic pregnancies and the serum levels of 17 beta-estradiol and estetrol were assayed before and at 15 or 30-minute intervals for three hours after the injection. All tests were carried out during the 25th to 36th week of amenorrhea. Serum estradiol rose rapidly in normal subjects and remained high to the end of the test. In patients with gestational pathology the estradiol pattern was not significantly different from that of the controls. Esterol plasma levels showed a biphasic pattern with an initial rise at 30 min. and a second rise at 90 min. in normal pregnancies, whereas in pathologic pregnancies this response was either lacking completely or was markedly reduced compared to the controls.

[Hormonal dynamics during pregnancy: critical discussion and clinical interpretations]. / Explorations hormonales dynamiques durant la grossesse: critique et interprétations cliniques.

Although the clinical interpretation of its results varies greatly among perinatologists, the dehydroepiandrosterone sulfate (DHEA-S) loading test has become an integral part of fetal monitoring in many centres dealing with high-risk pregnancies. Currently four main metabolic responses to administration of DHEA-S to the mother are monitored to predict the functional state of the fetoplacental unit: the metabolic clearance of DHEA-S, the metabolic clearance of DHEA-S into estradiol, the conversion of DHEA-S into estradiol or esterol, and the increase in the plasma concentrations of DHEA and androstenedione after administration of DHEA-S. This article critically reviews each of these responses and its possible clinical interpretation, and assesses the clinical future of the DHEA-S loading test.

PIP: The dehydroepiandrosterone sulfate (DHEA-S) loading test is increasingly used to detect fetal disorders in high risk pregnancies. There are 4 types of metabolic responses to the injection of DHEA-S: 1) metabolic clearance of DHEA-S, which represents the proportion between production and plasma concentrations of DHEA-S; 2) metabolic clearance of DHEA-S into estradiol, which presupposes the utilization of radioactive materials and is, therefore, unadvisable; 3) metabolic conversion of DHEA-S into estrogens, which can be measured in the urine or in the blood plasma; and 4) increase in the plasma concentrations of DHEA-S and androstenedione, caused by the enzymatic process implied in the conversion of DHEA-S into estrogens. The clinical interpretations of the DHEA-S test is very limited and controversial, and its application cannot yet replace the other methods of antenatal investigation.