IN VITRO CONVERSION OF [4-14C] DEHYDROEPIANDROSTERONE AND ANDROSTENEDIONE TO OESTROGENS BY THE MICROSOMES OF PLACENTAS FROM NORMAL, TOXAEMIC, DIABETIC AND POSTMATURE PREGNANCIES

Abstract

ABSTRACT The placental oestrogen precursors [4-14C]dehydroepiandrosterone (DHA) and [4-14C]androstenedione (AD) were incubated with microsomal fractions of human placentas from normal and pathological pregnancies at different stages of gestation, in order to evaluate the rate of conversion of the substrates to oestrogens. In placentas from normal pregnancies the capability to convert C19-steroids (DHA and AD) to C18-steroids (oestrone and oestradiol017β) increased with the age of gestation. The placenta at term metabolizes [4-14C]DHA and [4-14C]AD into oestrogens (oestrone and oestradiol-17β) with a four times greater aromatisation rate than the placenta at midpregnancy. The concentration of protein in the placental microsomal fraction also increased with the age of gestation. In our aromatisation studies it was found that the conversion rate of DHA and AD to oestrogens (oestrone and oestradiol-17β) by placental microsomes was significantly lowered in toxaemic and diabetic placentas and in placentas of postmaturity cases as compared to normal placentas at term. The relationship between placental insufficiency and a lowered capacity of Δ5-Δ4-isomerase, 3β-hydroxysteriod-dehydrogenase and the aromatizing enzyme systems is discussed with regard to the main causes of a low oestriol excretion and a low aromatisation rate of injected DHA-S in pathological pregnancies. Finally it is shown, that the parameters of the hormonal investigations correlate with the degree of pathological microscopic alterations of the placentas.