Regulation of 17 beta-estradiol synthesis in the proestrous hamster: role of progesterone and luteinizing hormone

Abstract

In hamsters, after the LH surge on proestrus, there is a shift in the pattern of ovarian steroidogenesis involving an abrupt decline in serum estrogen and testosterone (T) and a concomitant increase in serum progesterone (P). The present study examined the roles of LH and P in controlling ovarian 17β - estradiol (E2) production using in vivo and in vitro methods. The administration of 10-200 jug P at 1000 h on proestrus consistently depressed serum E2 within 1 h. The decline in serum E2 continued for the subsequent 3 h. Thereafter, serum E2 increased in response to the endogenous LH surge, since the rise in E2 could be prevented by the administration of phenobarbitol. The decline in serum E2 after exogenous P at 1000 h was not always associated with a decline in serum LH or FSH. For instance, serum LH was the same in hamsters treated with 10 jug P and in controls between 1100-1800 h. Serum FSH, however, declined slightly but only during the first hour. The injection of 50 ng P at 1000 h had no significant effect on serum levels of androstenedione (A) and T. The injection of 17a-hydroxyprogesterone 17a-0HP), A, or T had no effect on serum E2, indicating the specific effect of P in depressing serum E2. Simultaneousinjection of T along with P was able to prevent the fall in 2 levels during the first hour only. These results suggest that the synthesis of follicular estrogen in proestrous hamsters is very sensitive to P and that P may serve as an intraovarian regulator of estrogen synthesis. However, contrary to the situation in vivo, the addition of P in vitro greatly enhanced E2 production (838 ± 27 pg/mg-h) during a 2-h incubation The injection of 10 jug LH (NIH-S-16) sc at 1000 h on proestrus significantly elevated serum E2 (267 ± 11 pg/ml) within 1 h, followed by a steady decline during the subsequent hours. Bythe end of the fifth hour, serum E2 was very much reduced (47 ± 6 pg/ml). Similarly, serum T increased significantly during the first hour (358 ± 28 pg/ml) an then declined steadily, paralleling the declining E2. On the other hand, P levels progressively increased (from 1 to 17 ng/ml serum) during the entire 5-h period. In the in vitro system, LH (250 ng/ml) stimulated E2 production during the entire 4-h incubation, since t he production of E2 (as measured in the medium) was the same at the end of the first 2 h (2147 ± 257 pg/mg/ml) and at the end of the second2 h (1745 ±173 pg/mg/ml). Thus, in vitro, LH sustained E2 synthesis, whereas LH led to a rapid decline in serum E2 in vivo. The fall in serum E2 in normal hamsters begins at 1600 h on proestrus. Attempts were made to prevent this decline by administering P, 17a-0HP, A or T at 1300 h. The injection of 500 jug T prevented the fall in serum E2, at least until 1800 h. A low dose of T (50 /xg) as well as 500 jug P and 17a-0HP were unable to prevent the fall in E2, while A was partially effective. These results indic te that in the hamster, T is a more readily aromatizable androgen and that higher T levels are robably needed for the maintenance of the aromatase system. These results also suggest a possible block in steroidogenesis at some point past 17-hydroxylation The fact that the inhibitory effects of P were brought about much earlier than LH suggests that inhibitory effects of LH on E < synthesis are most likely mediated through P. The presentstudies, therefore, suggest that in the hamster, LH has primarily a stimulatory action on steroidogenesis, and its inhibitory effects on E2 synthesis are secondarily manifested through P or another factor(s) unknown at present.