Identification and Determination of Neutral Steroid Sulphates in Human Foetal Adrenal and Liver Tissue

Abstract

The endogenous neutral steroids in adrenal and liver tissue obtained from foetuses of 12\p=n-\17 weeks gestation were investigated. After extractions, the steroids were fractionated into a monosulphate and a disulphate fraction on Sephadex LH-20. The conjugates were cleaved by solvolysis, and purified on silicic acid and their trimethyl silyl ethers were analysed by gas-liquid chromatography and gas chromatography-mass spectrometry. Only neutral steroid monosulphates were found. The following compounds were identified in the monosulphate fraction of adrenal tissue: dehydroepiandrosterone, 16\g=a\-hydroxydehydroepiandrosterone, pregnenolone and 17\g=a\-hydroxypregnenolone,and of liver tissue; dehydroepiandrosterone, 16\g=a\-hydroxydehydroepiandrosterone, androst-5-ene\x=req-\ 3 \ g = b \ , 1 6 \ g = a \ , 1 7 \ g = b \ -t r i o l , pregnenolone, 17\g=a\-hydroxypregnenoloneand 16\g=a\-hydroxypregnenolone. The identifications and the results of the quantitative determinations of endogenous neutral steroid sulphates suggest that pregnenolone is synthesised in vivo in the foetal adrenal and converted to 17\g=a\-hydroxypregnenoloneand dehydroepiandrosterone sulphates. The latter compound is further transformed to 16\g=a\-hydroxydehydroepiandrosterone sulphate. No 16\g=a\-hydroxylationof pregnenolone was observed in adrenal tissue, whereas liver tissue seems to form 16\g=a\-hydroxypregnenolone. Reduction of a 17-keto group to 17\g=b\-hydroxyl and a 20\ x=req-\ keto group to 20\g=a\-hydroxyl seems to take place in liver but not in adrenal tissue.

Studies on the Metabolism of Steroids in the Foetus

“…The isolation of testosterone from androstenedione confirms the findings of Benagiano et al [3] and Huhtaniemi et al [14] that an extensive interconversion of both steroids occurs in the foetal life. The study of the metabolism of these two ClgO,-steroids in the human foetal liver assumes to be important since they are potential precursors of most of the ClgO, and C,,O,-steroids identified in the late pregnancy urine.…”

Secretion of Free and Sulfate-Conjugated Neutral Steroids by the Human Testis. Effect of Administration of Human Chorionic Gonadotropin1

“…1) was identified as androstenedione (17). Compound 7 was found to be 17o;-hydroxypregnenolone (18) and the derivatives of compound 8 gave RRT values and mass spectra identical with those of the corresponding derivatives of 17a-hydroxyprogesterone.…”

Effect of Maternal Intrahepatic Cholestasis on Fetal Steroid Metabolism

“…The fetus synthesizes steroids from acetate via "the conjugating pathway" and thus produces pregnenolone and dehydroepiandrosterone sulfates (18,19). The fetal liver hydroxylates steroids in the 16a-position (20) and is regarded as the main site of production of 16a-hydroxypregnenolone and 16a-hydroxydehydroepiandrosterone (20,21). The fetal origin of these steroid conjugates is confirmed by the higher levels of dehydroepiandrosterone (22), 16a-hydroxydehydroepiandrosterone (23,24), and 16a-hydroxypregnenolone (24) sulfates in the umbilical artery, as compared with umbilical venous blood.…”