Control of Aromatase Activity in Luteal and Ovarian Nonluteal Tissue of Pregnant Rats*

Abstract

The purpose of this investigation was to determine the aromatizing capacity of luteal and nonluteal tissues throughout the second half of pregnancy and to find out what regulates the aromatizing systems in both the corpora lutea and ovarian nonluteal tissues of the pregnant rat. Luteal and nonluteal tissues obtained between days 12–22 of pregnancy were incubated for 4 h in vitro with testosterone (T) substrate. The net synthesis of 17β-estradiol (E) was masured as an index of aromatase activity. Corpora lutea isolated on all days of pregnancy exhibited a striking capacity to convert T to E. The aromatizing capacity of luteal tissue increased significantly from day 12 through day 15, then declined steadily until the end of pregnancy. The nonluteal tissue synthesized significantly less E than the luteal tissue, with the levels of E produced remaining constant through day 19 and increasing by day 22. Hypophysectomy on day 12 of pregnancy resulted in a complete loss of aromatase activity in nonluteal tissue and concomitantly induced a significant increase in the aromatizing capacity of the luteal tissue. By day 22, corpora lutea of hypophysectomized rats synthesized 2.5 times more E than that of intact controls. To determine whether the drop in aromatase activity in the nonluteal tissue and its increase in luteal tissue after hypophysectomy was due to the absence of FSH, rats hypophysectomized on day 12 were injected daily with 10 μg FSH. In vivo administration of FSH reversed the effect of hypophysectomy on E production by nonluteal tissue, but had no inhibitory action on luteal aromatase. Removal of placentas from hypophysectomized rats was followed by a dramatic decline in the aromatizing capacity of luteal cells. Nevertheless, corpora lutea that ceased to produce progesterone (P) remained capable of producing as much E as the nonluteal tissue of intact animals. Since the placenta maintains the ovarian production of both T and P, it was of interest to determine whether its stimulatory effect on luteal aromatase was mediated by these steroids. Pregnant rats were hypophysectomized and hysterectomized on day 12 and treated between days 12–21 with 8 mg P daily or with T released from 1-cm capsule. Luteal aromatase was measured on days 14, 19, and 22 of pregnancy. On these days, treatments with either P or T stimulated luteal aromatase activity to levels found in intact controls. Treatment with T stimulated the production of P on day 14 only, but sustained the luteal aromatase activity long after the corpora lutea ceased to produce P. In contrast, neither steroid had an effect on nonluteal cell aromatase. However, when administered along with FSH, T enhanced and P diminished the ability of FSH to stimulate the nonluteal tissue aromatase. The results of this study indicate that the luteal tissue of pregnant rats possesses a more active aromatase then the nonluteal tissue and retains its aromatizing capacity long after the tissue ceases to secrete P. These results further demonstrate that luteal aromatase is not controlled by FSH but is stimulated by both T and P. The stimulatory effect of FSH on nonluteal tissue is enhanced by T and inhibited by P. Thus, P produced during pregnancy acts at two ovarian loci to either enhance or inhibit aromatase activity.