Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [14C] and [3H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer.
Sulfatase and 11β-hydroxysteroid dehydrogenase activities of human placenta were studied with respect to four steroids of the pregn-4-ene C-21-yl-sulfate series. Homogenates, as well as the microsomal fraction of placenta obtained either at midterm or at term, possessed negligible sulfatase activity with respect to the sulfates of 11-dehydrocorticosterone and corticosterone, and low but consistent activity towards 11-deoxycorticosterone sulfate. Under the same conditions dehydroepiandrosterone sulfate was hydrolyzed almost quantitatively.Placental homogenates converted cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. The reaction was greatly enhanced by the addition of NADP. In contrast, the corresponding 11β-hydroxy-C-21 steroid sulfates were poor substrates with respect to placental 11β-hydroxysteroid dehydrogenase, as indicated by the low yields of the sulfates of cortisone and 11-dehydrocorticosterone, even in the presence of NADP. These findings are consistent with the pattern of steroids of the pregn-4-ene series characterized in human cord plasma.
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