Synthesis of Steroids in the Newborn Human Adrenalin Vitro

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Abstract
Adrenals from a hydrocephalic newborn infant and from an adult undergoing adrenalectomy for mammary carcinoma were homogenized and incubated with progesterone-4-C14 or pregnenolone-7[alpha]-H3. The percentage of substrate converted to product was calculated from the specific activity of the final product isolated after gradient elution chromatography on celite columns, countercurrent distributions and re crystallizations to constant specific activity. A derivative of some of the products was made and recrystallized. The addition of an NADPH (nicotinamide adenine dinucleotide phosphate, reduced form)-generating system increased the conversion of progesterone to cortisol, decreased its conversion to corticosterone and deoxycorticosterone, but had little or no effect on the 16-hydroxy-lation of progesterone. Very little androstenedione was formed from progesterone in any of the 3 incubations. Pregnenolone was metabolized by the newborn adrenal to cortisol, androstenedione, corticosterone, progesterone, dehydroepiandrosterone, 17-hydroxypregnenolone and 16-hydroxypregnenolone. The addition of an NADPH-generating system decreased the production of cortisol but increased the production of androstenedione. These findings are inconsistent with the hypothesis that progesterone is an obligatory intermediate in the synthesis of cortisol and androstenedione from pregnenolone in normal newborn adrenals in vitro. When the adrenal of a newborn infant was incubated in vitro, sizable amounts of androstenedione were found, whereas very little was isolated when homogenates of adult adrenals were incubated under identical conditions. Thus, under the in vitro conditions employed, there appeared to be quantitative but not qualitative differences between newborn and adult adrenals in the enzymes concerned with steroid biosynthesis.