Progesterone Regulation of Estrogen Receptor in the Hamster Uterus during the Estrous Cycle*

Abstract

The purpose of this study was to determine serum steroid-uterine receptor relationships during the preovulatory period of the hamster estrous cycle. Methods were developed and validated for the simultaneous measurement of estrogen receptor (Re) and progesterone receptor in cytosol and a KCl extract of the nuclear fraction. Receptor levels (picomoles per g tissue) were determined by Scatchard plot analysis of specific ³H-labeled steroid binding data. Serum 17β-estradiol (E) and progesterone (P) were measured by standard RIA procedures. During the 4-day cycle, nuclear Re increased from day 2 to the morning of day 4 (proestrus) in parallel with rising serum E titers. After the critical period (1300–1400 h) for the ovulatory surge of gonadotropin on day 4, there was a transient surge of serum E and a sustained elevation of serum P. Preovulatory P secretion was associated with P receptor translocation to the nuclear fraction. The E surge was accompanied by cytosol Re depletion, but there was no concomitant increase in nuclear Re. Nuclear Re levels dropped abruptly 2–4 h after the serum E peak. These results suggested that the reduction in nuclear Re might be due to either E withdrawal or P action. To test these two possibilities, experiments were performed with ovariectomized animals bearing sc implants of Silastic tubes containing crystalline E. Removal of E implants (E withdrawal) altered subcellular Re distribution with no net change in total Re over an 8-h period, i.e. cytosol Re increased and nuclear Re decreased. In contrast, P treatment (2.5 mg/100 g BW) with serum E maintenance caused a rapid (2–4 h) reduction in both cytosol and nuclear Re. Combined E withdrawal and P treatment decreased nuclear Re but not cytosol Re. Thus, P action selectively reduced nuclear Re, while cytosol Re depletion was primarily regulated by the serum E level. Furthermore, the nuclear Re response to P was dose dependent and specific for progestogenic steroids. These findings indicate that P action is responsible for the rapid reduction in uterine nuclear Re observed during the preovulatory period in the cyclic hamster, and that this effect of P on nuclear Re may represent a fundamental mechanism for P modulation of estrogen action.