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Title: Why so much oestriol? A comparison of the aromatisation of androstenedione and 16 alpha-hydroxyandrostenedione when incubated alone or together with human placental microsomes. Author: Othman YS, Oakey RE. Journal: J Endocrinol; 1996 Mar; 148(3):399-407. PubMed ID: 8778218. Abstract: Estimates of the relative abundance of 16 alpha-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 16 alpha-hydroxydehydroepiandrosterone sulphate and dehydroepiandrosterone sulphate in cord blood is about 2.5:1. This discrepancy might imply that 16 alpha-hydroxy-C19 steroids are used more efficiently for placental oestrogen biosynthesis than are the 16 alpha-deoxy-C19 steroids. On testing this hypothesis by incubation of placental microsomes with 16 alpha-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 16 alpha-hydroxy-C19 steroid (Michaelis constant, (Km) 0.75-1.24 mumol/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 mumol/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 16 alpha-hydroxyoestrogens additional to placental aromatisation need to be considered. Hydroxylation of 16-deoxyoestrogens (the phenolic pathway) appears limited but aromatisation in fetal liver of 16 alpha-hydroxyandrostenedione not utilised by the placenta appears to be worth attention.[Abstract] [Full Text] [Related] [New Search]