Estrogen Synthesis by the Pregnant Baboon

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Abstract
The baboon (Papio anubis) has been evaluated as a model for studying the control of estrogen synthesis during human pregnancy. Conversion of intravenously administered 3^H-DHA (3β-hydroxyandrost-5- ene-17-one) and 3^H-DHAS (androst-5-en-17-one-3β-y 1 sulfate) to urinary estrone, estradiol-17^ and estriol and to estradiol-17β at the tissue level increases throughout gestation. The extent of conversion of DHAS was approximately one tenth of that observed in humans, suggesting limited placental biosynthetic capacity. Incorporation of 3H from both precursors into estrone exceeded that into estradiol-17β 6-fold and into estriol > 12-fold. This parallels the metabolism of intravenously administered 14^C-estradiol-17β and quantitative estrogen excretion patterns in this species. Incorporation of 3^H into estrogens was 2-8 times more extensive from DHA than from DHAS, as is the case in human placental perfusions. Determination of placental enzyme activities involved in estrogen synthesis indicated that steroid-3-sulfatase > 3β-hydroxysteroid dehydrogenase-isomerase > aromatase, which is also true for human placentae, but baboon aromatase levels were relatively lower. Structure-activity correlations for inhibition of baboon and human placental sulfatase by naturally occurring steroids are similar. The baboon is a promising model to study control mechanisms generally and to examine our suggestion that inhibition of placental sulfatase by endogenous steroids renders it rate-limiting and may control estrogen synthesis from conjugated precursors in vivo.

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