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In order to clarify some of the developmental processes of the human adrenal cortex or steroidogenesis in infancy and childhood, serum concentrations of 17-hydroxypregnenolone, 17-hydroxypregnenolone sulfate and 17-hydroxyprogesterone were measured by means of a combined radioimmunoassay method, and the age-related changes in these steroids were also examined. The actual ranges of serum concentrations of 17-hydroxypregnenolone, 17-hydroxypregnenolone sulfate and 17-hydroxyprogesterone in umbilical cord blood were 27.1-80.5, 1,560-5,030 and 53.3-304 nmol/l, respectively. These values subsequently decreased to nadirs of 0.95-2.09 nmol/l of 17-hydroxypregnenolone in subjects 1 to 2 years old, 0.93-7.03 nmool/l of 17-hydroxypregnenolone sulfate in subjects 3 to 6 years old and 0.18-0.78 nmol/l of 17-hydroxyprogesterone in subjects 1 to 2 years old, respectively, and they were followed by gradual increases to the adult levels. This study thus revealed the age-related changes in 17-hydroxypregnenolone and its sulfate concentrations in infancy and childhood and indicated that, in the process in which the adrenal cortex was differentiated to the definitive form, the decrease in the activity of steroid sulfotransferase in infancy and childhood occurred more slowly than the increase in that of 3 beta-hydroxysteroid dehydrogenase.

In order to clarify a part of the developmental processes of the human adrenal cortex or steroidgenesis in infancy and childhood, serum concentrations of 17 alpha-hydroxypregnenolone (17-OH-delta 5 P), 17 alpha-hydroxypregnenolone-3-sulfate (17-OH-delta 5 P-S) and 17 alpha-hydroxyprogesterone (17-OH-delta 4 P) were measured using a combined radioimmunoassay method previously reported, and age-related changes of these steroids were evaluated. In addition to the serum concentrations, a ratio of 17-OH-delta 5 P-S to 17-OH-delta 5 P (S/delta 5 P ratio) and that of 17-OH-delta 4 P to 17-OH-delta 5 P (delta 4 P/delta 5 P ratio) were also estimated as the indices of the activities of steroid sulfokinase (SK) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), respectively. Serum 17-OH-delta 5 P, 17-OH-delta 5 P-S and 17-OH-delta 4 P concentrations in umbilical cord blood were 13.5 +/- 6.02 (Mean +/- SD) ng/ml, 965 +/- 363 ng/ml and 46.3 +/- 21.1 ng/ml, respectively. These values decreased consecutively to the nadirs which were 0.47 +/- 0.16 ng/ml in subjects 1 to 2 years old, 1.26 +/- 0.82 ng/ml in subjects 3 to 6 years old and 0.17 +/- 0.007 ng/ml in subjects 3 to 4 months old, respectively, and they were followed by gradual increases up to the adult levels. S/delta 5 P ratio also showed the same profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum concentrations of 17-hydroxypregnenolone, 17-hydroxypregnenolone sulfate and 17-hydroxyprogesterone were measured simultaneously in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, using a combined radioimmunoassay method. All these precursor steroids were found to be markedly elevated in the sera of untreated patients with a salt-losing form of the disease, whereas, in untreated patients with a simple virilizing form, only the concentration of unconjugated steroids was increased and the 17-hydroxypregnenolone sulfate concentration remained within the normal range. Among the patients with a salt-losing form under maintenance therapy, these steroids were all still significantly increased in those on insufficient control, whereas only 17-hydroxyprogesterone was significantly but slightly increased in those on adequate control. Although the mechanism whereby the serum 17-hydroxypregnenolone sulfate concentration is not increased in the untreated simple virilizers is unknown, both a milder degree of 21-hydroxylase deficiency and a role of 17-hydroxypregnenolone sulfate in adrenal steroid production as a kind of supplier are suggested as possible explanations, especially in the neonatal period and early infancy. Thus, this study showed the serum concentrations of 17-hydroxypregnenolone and its sulfate together with 17-hydroxyprogesterone in patients with 21-hydroxylase deficiency in various conditions.

It is well recognized that in the fetal adrenal cortex, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is lower and in fetal tissues, steroid sulfokinase (SK) is higher than in the adult. In order to clarify a part of the development processes of the adrenal cortex or steroidgenesis in humans, a combined radioimmunoassay (RIA) method to estimate serum 17 alpha-hydroxypregnenolone (17-OH-delta 5 P), 17 alpha-hydroxypregnenolone sulfate (17-OH-delta 5 P-S) and 17 alpha-hydroxyprogesterone (17-OH-delta 4P) was devised. The method consisted of the following procedures: 1) diethyl ether extraction and chromatographic separation of unconjugated steroids (17-OH-delta 5P and 17-OH-delta 4P), 2) enzymatic hydrolysis of 17-OH-delta 5P-S using the residue of diethyl ether extraction for a material, 3) diethyl ether extraction and chromatographic purification of hydrolyzed 17-OH-delta 5P-S, and 4) RIAs for 17-OH-delta 5-P to estimate 17-OH-delta 5P and 17-OH-delta 5P-S concentration, and for 17-OH-delta 4P. Extracted 17-OH-delta 5P was well separated from 17-OH-delta 4P by Sephadex LH-20 microcolumn chromatography, using a benzene/methanol = 95/5 (v/v) solvent as a mobile phase. Several procedures for hydrolysis or solvolysis of 17-OH-delta 5P-S were compared using available tritiated delta 5-3 beta-hydroxysteroids including dehydroepiandrosterone (DHA), DHA sulfate (DHA-S) and 17-OH-delta 5P, and it was found that the most suitable method was an enzymatic hydrolysis by arylsulfatase from Helix Pomatia in an appropriate condition in which the percent hydrolysis was 92.9 +/- 1.2 (mean +/- SEM)%. The final percent recoveries were 88.7 +/- 1.2% in 17-OH-delta 4P, 90.7 +/- 1.4% in 17-OH-delta 5P and 78.1 +/- 2.1% in 17-OH-delta 5P-S, respectively. A suitable antiserum and its final dilution titer for RIA of 17-OH-delta 5P (hydrolyzed 17-OH-delta 5P-S also) was 1:12,000 dilution of anti-17-OH-delta 5P-3-succinate-BSA serum. An anti-7-oxo-17-OH-delta 5P-7-carboxymethyloxime-BSA serum was considered to be unsuitable for the measurement of hydrolyzed 17-OH-delta 5-P-S, presumably because of a significant cross-reactivity with a large amount of unknown steroid sulfates simultaneously hydrolyzed.(ABSTRACT TRUNCATED AT 400 WORDS)