The in vitro formation of sulfates and glucuronides of estrogens by adult and fetal ovine tissues

Abstract

Incubation of nanomolar concentrations of [3H]estrone with ovine liver slices from adult and fetal animals demonstrated, in particular, the production of estrogen sulfates together with smaller amounts of glucuronides, even although microsomal estrogen glucuronyltransferase (GT) and sulfatase activities were high, especially in adult tissue. [3H]Estriol was conjugated almost exclusively as sulfate under the same experimental conditions. Slices of maternal and fetal kidney medulla were also strikingly active in promoting estrogen sulfate production as were slices of fetal kidney cortex. Adult kidney cortex conjugated estrogen only in the glucuronide form. These data indicate the possibility that maternal and fetal liver and kidney might contribute to the high circulating level of estrone sulfate in the pregnant sheep. Through the use of [3H]estrone and [3H]estrone sulfate as substrates, it was possible to demonstrate that adult slices of kidney medulla possessed relatively low sulfatase, considerable sulfotransferase (ST), and virtually no GT activity, whereas cortex had high sulfatase, little or no ST, and low, though demonstrable, GT activity. The ST activity of kidney high-speed supernatants was stimulated by the presence of sulfhydryl groups, whereas that in liver was not. Enzymic reduction of estrone and (or) estrone sulfate by liver and kidney slices indicated that, in the former, 17 alpha-reduction prevailed and, in the latter with the exception of the maternal medulla, 17 beta-reduction was the main pathway, particularly in the fetus.

Regulation of Steroid Hormone Action in Target Cells by Specific Hormone-Inactivating Enzymes

“…Although most of this article has been concerned with hormone inactivation through oxidoreduction (23,47) and sulfurylation (48), there are many other enzymatic reactions that can potentially be used to inactivate steroid hormones. One such reaction is hormone-specific glucuronidation, which has not been examined carefully (49). In addition, sulfurylation of the steroid hormone can also serve as a storage form of the hormonal steroid, and its reactivation through specific steroid sulfatases may contribute to an efficient hormonal homeostasis (49,50).…”

“…One such reaction is hormone-specific glucuronidation, which has not been examined carefully (49). In addition, sulfurylation of the steroid hormone can also serve as a storage form of the hormonal steroid, and its reactivation through specific steroid sulfatases may contribute to an efficient hormonal homeostasis (49,50). Specific estrone sulfate sulfatase and dehydroepiandrosterone sulfate sulfatase have been identified in breast cancer cells, endometrium, hypothalamus.…”