Synthesis, metabolism and secretion of estrogens in the human term placenta

This dissertation describes studies of metabolism and distribution of estrogens in the human placenta, conducted both at the subcellular and the whole organ levels. Initially, preparations of microvillar membranes were employed to successfully search for plasma for plasma membrane associated enzymes involved in steroid metabolism (17β dehydrogenases and sulfatases). Differences in kinetic characteristics for the dehydrogenation at C-17 of testosterone (T) and estradiol (E2) were found in microvillar, microsomal, cytosolic and mitochondrial fractions. Although placental microvilli were a rich source of steroid metabolizing enzymes, specific binders for E2 were not found at this site. In experiments in which labeled estrone (E1), E2, and estriol (E3) were generated within the syncytium during simultaneous maternal and fetal perfusion of isolated term placentas with unconjugated precursors, two major observations were made: (1) the distribution of 3H-E1, 3H-E2, and 3H-E3 between fetal and maternal perfusates was unexpectedly different for each compounds and (2) ethynyl estradiol (EE), a competitor of estrogen binding, provoked a large and selective release of 3H-E2 to the fetal perfusate in placentas labeled with E1 and E2. These data are consistent with a model which depicts both the binding and metabolism of E2 at sites within the capillary endothelium. It was suggested that steroid binding and/or metabolizing activities at the level of the microvillar membrane or capillary endothelium can influence the amount and potency of estrogen delivered to mother and fetus