Kinetic Analysis of Adrenal 3β-Hydroxysteroid Dehydrogenase Activity During Human Development*

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Abstract
Kinetic analyses of microsomal 3β-hydroxysteroid dehydrogenase (3β-HSD) activity in adrenal glands from 11 individuals, aged 1–60 yr, were carried out to determine whether changes in substrate or cofactor affinity (Km) or cellular content, as reflected in maximal velocity, could explain the changes in adrenal Δ5-3β-hydroxysteroid secretion that occur in late childhood and puberty. The Km values for the cofactor NAD+ were similar regardless which substrate, dehydroepiandrosterone (DHA), pregneholone, or 17-hydroxypregnenolone (17OH-Δ5P), was used. The Km values for DHA (0.3 µM), pregnenolone (0.4 µM), and 17OH-Δ5P (0.3 µM) were similar and within the intraadrenal concentration ranges for DHA and 17OH-Δ5P previously reported. Each substrate was a competitive inhibitor for the others, with close similarity between affinity and inhibition constants. These observations point to the presence of a single 3β-HSD, rather than several substrate-specific variants. There was no change in substrate Km with age; the maximal velocity was lower (0.1–0.6 nmol/mg-min) in a single 1-yr-old infant than in later life, but there was no significant change (mean, 2.9–4.6 nmol/mg-min for the three substrates) between values at 12 and 60 yr. This suggests that ACTH-mediated induction of 3β-HSD may be low in infancy and higher in adults, while in vivo studies point to a reduction in actual 3β-HSD activity during this period. The likely explanation for this paradox between enzyme levels and final activity is that 3β-HSD is progressively inhibited during late childhood and puberty by rising intraadrenal concentrations of various Δ4-3-ketosteroids. (J. Clin Endocrinol Metab60: 934,1985)

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