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SUMMARY
Plasma levels of testosterone, androst-4-ene-3,17-dione, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) were estimated both before and after administration of clomiphene citrate to endocrinologically normal boys aged from 2–16 yr and to boys with adrenocortical hypofunction or hypogonadism. A divided daily dose of 200 mg/1·7 m2 of surface area was maintained for 15 days. The unconjugated steroids were measured by means of a double isotope derivative technique and the sulphates by gas-liquid chromatography.
The boys without testicular anomaly who were well established in puberty responded with a rise in plasma testosterone. In contrast, prepubertal boys showed a statistically significant decrease in plasma testosterone levels.
A concomitant finding was a significant rise in the plasma levels of androstenedione, DHA and DHAS. It is concluded that clomiphene does not liberate luteinizing hormone before puberty but it may well diminish its secretion. A secondary effect of clomiphene is the stimulation of adrenal C19-steroid production.
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SUMMARY
A method is described for the separation and estimation of neutral steroids in infant urine. The free steroids are obtained by a two-stage enzyme hydrolysis. Following preliminary chromatography, the extracts containing steroids of low and medium polarity are suitable for final resolution. The extract containing steroids of high polarity requires further purification by partition between ether-ethanol and aqueous ammonium sulphate, followed by reversed-phase paper chromatography. Final resolution of steroids in fractions of different polarity is achieved using Bush aqueous methanol systems. Losses incurred in the method are estimated by the use of 4-14C steroids.
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SUMMARY
Following enzyme hydrolysis of the urine of infants aged 1 to 6 days, the neutral steroids have been extracted and their excretion patterns determined using a method based on paper chromatography. Three groups of compounds have been estimated—those reacting with Zimmermann reagent, those reducing blue tetrazolium and those giving sodium fluorescence. The first group includes the 17-oxosteroids and the latter two the corticoids. The steroid excretion patterns in the urine of these infants have been compared with those demonstrated by the same technique in adult female urine and in the urine of mothers in the 24 hr. following delivery.
For all groups of compounds, the excretion patterns in the urine of infants are different from those found in the urine of their mothers or in that of adult women. The outstanding feature in infant urine is the dominance of compounds which behave like steroids, and which either do not occur in adult urine, or are present in insignificant amounts. Less obvious changes in the excretion patterns of 17-oxosteroids and of corticoids in pregnancy urine are also described.
Many of the Zimmermann chromogens which are dominant in the urine in the first days of life have greatly diminished, or have disappeared, by the 6th day. This applies both to full-term and premature infants.
The pattern of excretion of blue tetrazolium-reducing material in the urine of newborn infants is extremely complicated and, apparently, unique. Tetrahydrocortisol and tetrahydrocortisone, which are the major corticoid metabolites in adult urine, are much less prominent in the urine in the first 3 days of life.
A blue tetrazolium-reducing steroid isolated from the urine of infants has been provisionally identified as 3β, 21-dihydroxypregn-5-ene-20-one.
The altered steroid excretion patterns found in the urine of newborn infants are thought to indicate that there are fundamental differences in the metabolism of adrenal and placental steroids which are peculiar to this period and comparable with those established within recent years for oestrogens and progesterone.