The effects of progesterone, pregnenolone, estriol, ACTH and hCG on steroid secretion of cultured human fetal adrenals

Abstract

Endogenous steroid secretion and the conversion of exogenous pregnenolone and progesterone were studied in tissue culture of human mid-term fetal adrenals. Addition of pregnenolone on the first day of cultivation caused an increase in DHAS (dehydroepiandrosterone sulphate) and pregnenolone sulphate secretion during the first cultivation days, but no significant increase in cortisol production was noted. Progesterone at the same stage of cultivation was effectively converted into cortisol indicating that human fetal adrenals in spite of the lack of 3β-HSD (3β-OH-steroid dehydrogenase) are capable of synthesizing efficiently cortisol using exogenous ( in vivo placental) progesterone as a substrate. During later stages of cultivation pregnenolone was converted into pregnenolone sulphate, but not into DHAS, indicating that sulphokinase activity is maintained in cultured adrenal cells. Estriol and estradiol-17β inhibited steroidogenesis in ACTH-stimulated tissue culture, and the inhibition step seemed to be 3β-HSD-step. The demanded concentrations of estrogens for significant inhibition were, however, unphysiological. Estriol-3-sulphate and DHAS did not inhibit steroidogenesis. hCG did not stimulate DHA or DHAS production, neither did it modify the stimulatory effect of ACTH towards these estrogen precursors.