16a-Hydroxydehydroepiandrosterone sulfate

Estriol is also produced by another pathway in the syncytiotrophoblast cells of the placenta DHEAS from fetal adrenal is converted to 16a-hydroxydehydroepiandrosterone sulfate in the fetal liver, followed by removal of the sulfated chain to produce 16a-hydroxy-dehydroepiandrosterone, which is then aromatized to estriol. Estriol is the predominant estrogen produced during pregnancy, and almost all of tiie estriol and estradiol produced by the placental syncytiotrophoblast enters the maternal circulation. By the 7th week of gestation, the placenta produces the majority of the estrogen in the maternal circulation. 

E2. Easterling, W. E., Jr., Simmer, H. H., Dignam, W. J., Frankland, M. V., and Naftolin, F., Dehydroepiandrosterone sulfate, 16a-hydroxydehydroepiandroste-rone and 16a-hydroxydehydroepiandrosterone sulfate in maternal and fetal blood of pregnancies with anencephalic and normal fetuses. Steroids 8, 157-178 (1966). 

In vivo results have shown that dehydroepiandrosterone sulfate gives more 16a-hydroxydehydroepiandrosterone sulfate and androstenehiol sulfate than the corresponding reactions with free steroids, probably because dehydroepiandrosterone is rapidly transformed into androstene-dione, which is mostly reduced and hydroxylated only in small propor-... 

The transformations of 16a-hydroxydehydroepiandrosterone and 16a-hydroxydehydroepiandrosterone sulfate in the fetoplacental unit arc shown in Fig. 14. 

Roberts et ah (1964) answered part of the question by injecting doubly labeled cholesterol sulfate into the splenic artery (supplying 90% of the blood to an adrenal carcinoma) of a female patient and isolating various steroid sulfates in the urine of the first 24 hours. Of the recovered radioactivity 0.46% was dehydroepiandrosterone sulfate, bearing the same H/ S ratio as the injected compound. Urinary androstenediol-3-monosulfate and 5-pregnene-3/3,17a,20a-triol-3-monosulfate as well as 16a-hydroxydehydroepiandrosterone-3-monosulfate also had the same ratio as the injected cholesterol sulfate, demonstrating that all these compounds have a common sulfated precursor, which could possibly be cholesterol sulfate. 

Indirect and direct metabolism of dehydroepiandrosterone sulfate are combined in estrogen formation during pregnancy, since dehydroepiandrosterone sulfate is hydroxylated into 16a-hydroxydehydroepiandrosterone... 

As a result of the prolongation of the deficiency of the 3/3-hydroxy-dehydrogenase, As — A isomerase system after birth, an important quantity of 3 -hydroxy-As steroids is excreted in the urine of newborns. As the 16a-hydroxylase is very active in the first days of life, very little if any dehydroepiandrosterone or dehydroepiandrosterone sulfate is excreted in newborn urine (Migeon et al., 1957b Vestergaard, 1965 Bertrand et al., 1966 Paulsen et al., 1966) on the other hand, the total excretion rate of urinary 16a-hydroxydehydroepiandrosterone is 300-600 )tig/24 hours (Bongiovanni, 1962 Mitchell and Shackleton, 1966 Mitchell, 1967). Cleary and Pion (1968) found these values to be between 0.7 and 3 mg/24 hours in the first 2 days of life. Alost of these steroids arc eliminated as ester sulfates. 

---