Why so much oestriol? A comparison of the aromatisation of androstenedione and 16 alpha-hydroxyandrostenedione when incubated alone or together with human placental microsomes.
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.
Othman
Y S
YS
Division of Clinical Sciences, University of Leeds, UK.
Oakey
R E
RE
D000735:Androstenedione / Q000031:analogs & derivatives / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis; D004964:Estriol / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology*; D011863:Radioimmunoassay
D000735:Androstenedione; D004958:Estradiol; C018202:16-hydroxyandrost-4-en-3,17-dione; D001141:Aromatase; D004964:Estriol