A Specific Progesterone Receptor in the Hamster Uterus: Physiologic Properties and Regulation During the Estrous Cycle¹

Abstract

Our previous studies indicated the presence of an estrogen-dependent, progesteronebinding system in the hamster uterus. A progesterone- binding component has now been characterized in the uterine cytosol fraction by density gradient centrifugation (6–7S sedimentation coefficient in sucrose-glycerol gradients), binding equilibrium measurements (KA = 1.7 ± 0.08 × 109) M−1) and competition assays. The hormone specificity of the progesterone-binding component was indicated by the relative binding activity of progesterone (100), deoxycorticosterone (64) and 5α-pregnanedione (20). Other hormonal steroids tested or progesterone metabolites did not compete effectively for :3H-progesterone-binding sites. The concentration of progesterone-binding sites in uterine cytosol was calculated from Scatchard plot analysis of data obtained by a dextran-charcoal adsorption method. During the estrous cycle, fluctuations in the concentration of progesteronebinding sites on a wet weight, cytosol protein or DNA basis were correlated with the pattern of estradiol–17β and progesterone secretion. The cellular concentration of progesterone-binding sites increased during diestrus (day 3) to a maximum at proestrus on day 4 coincident with a rising serum estradiol level. The concentration of progesterone- binding sites decreased slowly after ovariectomy at proestrus and the level was rapidly restored by estrogen treatment, confirming that the elevation of uterine progesterone-binding sites during the cycle is estrogen dependent. The formation of a progesterone-binding component with a 6–7S sedimentation coefficient during the follicular phase of the cycle or following estrogen treatment in ovariectomized animals indicated this was the estrogen-responsive component of the uterine progesterone-binding system. The cellular concentration of progesterone-binding sites dropped markedly between proestrus and estrus on day 4 of the cycle which corresponded to the time of preovulatory progesterone secretion. This abrupt loss of progesterone-binding sites from the uterine cytosol fraction can be attributed to ovarian progestin action because a) it was inhibited by ovariectomy at proestrus, and b) progesterone treatment at proestrus caused a rapid premature depletion of binding sites. Associated with the progesterone-induced depletion of progesteronebinding sites was a reduction in 6–7S binding component. These results demonstrate that the 6–7S binding component possesses the characteristics of a hormone receptor which responds to the action of both estrogen and progestin during the hamster estrous cycle.(Endocrinology94: 1009, 1974)