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.

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In earlier investigations we have shown that administration of HCG to newborns stimulates the excretion of DHA in the urine of these children [9,10]. This increase in urinary DHA concentration by HCG Stimulation in vivo was even higher in prematures than in newborns at term. Perfusion studies by CHARLES demonstrated that HCG also increases the concentration of DHA in umbilical arterial blood in anencephalics [4]. Intrafetal injections of HCG in utero produced histological evidence of hormone biosynthetic Stimulation in the fetal adrenals [7]. HCG crosses to the fetus. It is found in higher concentration in the umbilical vein than in the arteries [8,9]. A rather high concentration of HCG has been found in fetal adrenal tissues by our group [12]. The concentration of HCG in the fetal organism is highest during the lOth-16th week post menstruationem when the fetal adrenals begin to function. The fetal adrenals are synthesizing DHA-S from the lOth-15th week of pregnancy on during which time a much sharper than normal increase in maternal estrogen excretion occurs [6]. The fetal pituitary production of ACTH begins at about the 16th week and increases up to the end of pregnancy [4, 15]. ACTH also stimulates the production of DHA-S and a great number of other Zl 5 -steroids and corticosteroids [10]. From these findings we were led to conclude that HCG might be a natural stimulator of the fetal zone X during the midtrimester of pregnancy, before the evolution of the hypothalamic-anterior pituitary axis occurs and ACTH successively takes over the Stimulation of the ripening fetal adrenals. l Material and methodsAll steroids were kindly given by MERCK (Darmstadt). (4-14 C)-DHA with a specific activity of 50 mCi/mMol and (4-14 C)-cholesterol with a specific activity of 50 mCi/mMol were supplied by the RADIOCHEMICAL CENTER AMERSHAM (Great Britain). All steroids were tested for their purity with paper and thin layer chromatography.

SUMMARY Chorionic gonadotrophin (HCG) concentrations were measured in newborn infants. The levels of HCG were found to be higher in the umbilical vein than in the arteries. The hormone is eliminated within 72 hr. post partum. After the injection of HCG a mean of 3·6% of the administered dose appeared in the urine. The renal clearance was very low (0·006 ml./min.) in the newborn corresponding to the low volume of urinary output. HCG is also excreted in the meconium and in the faeces during the first day of life. Administration of HCG to newborn infants significantly increased the urinary excretion of dehydroepiandrosterone. This rise was even more pronounced in premature infants. It is suggested that HCG is an adrenocorticotrophic hormone in the foetus, regulating the supply of foetal adrenal dehydroepiandrosterone as a precursor for the production of oestrogens in the placenta. The excretion of dehydroepiandrosterone in the urine of the newborn was found to lie between 78 and 277 μg./24 hr. After injection of sodium dehydroepiandrosterone sulphate, 5% of the dose was excreted in the urine. Dehydroepiandrosterone was not converted into oestrogens by the newborn.

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