The CONVERSION OF PREGNENOLONE TO PROGESTERONE AND 16α-Hydroxydehydroepiandrosterone IN VITRO BY ADRENAL TISSUE FROM a NEWBORN ANENCEPHALIC INFANT

Abstract

SUMMARY Adrenal tissue, largely composed of the definitive zone, from a newborn anencephalic infant, contained the following enzyme systems: (1) a Δ5-3β-hydroxysteroid dehydrogenase for pregnenolone, demonstrated by the conversion of [14C]pregnenolone to [14C]progesterone; (2) a C(17)-C(20) desmolase, and (3) a steroid 16α-hydroxylase, demonstrated by the conversion of [14C]pregnenolone to [14C]3β, 16α-dihydroxyandrost-5-en-17-one. The metabolites could not be separated from carrier steroids during sequential partition chromatography. [14C]Progesterone was identified by recrystallization to constant specific activity. [14C]3β, 16α-Dihydroxyandrost-5-en-17-one was identified by enzymatic conversion to [14C]16α-hydroxyoestrone followed by reduction to oestriol and determination of the specific activity of the oestriol after partition chromatography. It is suggested that these enzymes may play some part in the production of cortisol by the newborn anencephalic infant, and in the provision of precursors for placental oestriol production.

Steroids in Meconium from Male and Female Newborn Infants

“…The finding of this steroid is interesting in view of the results of Shahwan et al [32] indicating that adrenals from anencephalic foetuses may convert 3@,16a-dihydroxy-5-pregnen-20-one into the potential oestra-1,3,5( IO)-triene-3,16a,17~-triol (oestriol) precursor 313, 16a-dihydroxy-5-androsten-17-one. 19-Hydroxylation has previously been described in adrenals [33] and it is possible that the isolated steroid may be a metabolite of a 16,19-dihydroxylated C,, steroid that may serve as a substrate for oestra-1,3,5(10)-triene-3,16a, 1713-triol (oestriol) biosynthesis in the placenta.…”

Sterods in Newborns and Infants

“…However, this intermediate could not be found by Reynolds et al after injection of labelled 3/3,16a-and 38,17a-dihydroxypregn-5-en- [401. 20-one into the foetoplacental circulation [38]. Results obtained by Shahwan et al working with adrenal tissue from an anencephalic newborn indicate that 3j3-hydroxyandrost-5-en-17-one is not an obligatory precursor of 3B,16a-dihydroxypregn-5-en-17-one [43]. I n this case 16-hydroxylation must precede side chain cleavage and the 16,17-dihydroxylated steroid in faeces may be a reduction product of the proposed intermediate.…”

Corticosteroid Synthesis in Vitro by Adrenal Tissue From Newborn Anencephalic Infants

“…All chemicals, reagents and the procedures adopted for their purification, techniques for the determination of 3H, 14C and A4-3-oxo steroids, for acetylation, Division M. M. Shahwan, R. E. Oakey and S. R. Stitch hydrolysis and oxidation have been described previously (Shahwan et al 1968a [4-14C]cortisol. All radioactive steroids were purified by paper chromatography before use and were adjusted to an appropriate specific activity by addition of non-radioactive steroid.…”

“…The acetone was removed by distillation under reduced pressure in an atmosphere of nitrogen and the aqueous residue was extracted with ether (5 x 25 ml.). The ether was dried with sodium sulphate and a 'neutral steroid' fraction was prepared as described by Shahwan et al (1968a). The 'neutral steroid' fraction was chromatographed in system VI, and the individual metabolites were characterized by failure to separate radioactivity from authentic carrier steroid during a sequential purification procedure including multiple chromatography, derivative formation and crystalliza¬ tion.…”