Why so much oestriol? A comparison of the aromatisation of androstenedione and 16α-hydroxyandrostenedione when incubated alone or together with human placental microsomes

Abstract

Abstract Estimates of the relative abundance of 16α-hydroxy- and 16-deoxyoestrogens in late pregnancy urine lie between 13:1 and 5:1, yet the ratio of the concentrations of the major precursors 16α-hydroxydehydroepiandrosterone sulphate and dehydroepiandrosterone sulphate in cord blood is about 2·5:1. This discrepancy might imply that 16α-hydroxy-C19 steroids are used more efficiently for placental oestrogen biosynthesis than are the 16α-deoxy-C19 steroids. On testing this hypothesis by incubation of placental microsomes with 16α-hydroxy- and 16-deoxy- precursors together (concentration ratios 128:1 to 1:1), initial rates of oestrogen formation were highest from the 16-deoxy-C19 steroid. Additionally, whilst each substrate appeared to inhibit the aromatisation of the other, the 16-deoxy-C19 steroid was the more potent inhibitor. These findings were supported by an analogous experiment with placental slices. When each precursor was examined separately with microsomes from 4 placentae, aromatisation of the 16α-hydroxy-C19 steroid (Michaelis constant, (Km) 0·75–1·24 μmol/l, maximum reaction velocity (Vmax) 28–69 pmol product/min/mg protein) was less efficient than that of the 16-deoxy-C19 steroid (Km 0·10–0·15 μmol/l, Vmax 71–145 pmol product/min/mg protein). To reconcile the disparity between the measured utilisation of precursors in vitro and expectations drawn from precursor availability and urinary excretion rates, sources of urinary 16α-hydroxyoestrogens additional to placental aromatisation need to be considered. Hydroxylation of 16-deoxyoestrogens (the phenolic pathway) appears limited but aromatisation in fetal liver of 16α-hydroxyandrostenedione not utilised by the placenta appears to be worth attention. Journal of Endocrinology (1996) 148, 399–407