Hormonal control of progesterone receptors

Abstract

Uterine progesterone receptors are under dual hormonal control. Estrogen increases the concentration of receptor through a mechanism that depends on synthesis of both RNA and protein. Progesterone decreases the concentration of its own receptor, probably by enhancing its inactivation rate. This regulation explains receptor variations during the estrous cycle. In both guinea pig and rat uteri, cytosol receptor concentration is maximal at the preovulatory period and decreases after ovulation. Nuclear receptor was measured in the rat. Its concentration is also maximal at proestrus, but the higher nuclear to cytosol receptor ratio was observed at metestrus. There is a good correlation (r = 0.78) between nuclear receptor concentration, on one hand, and the product of cytosol receptor concentration times the plasma progesterone concentration, on the other hand. Autoradiographic studies show that receptor variations during the estrous cycle occur simultaneously in all cell types of uterine horn, cervix, and vagina, which suggests that similar mechanisms control receptor concentration in all of these cells. Progesterone receptor was also measured during pregnancy in rat uterus. Cytosol receptor concentration is low at the beginning of pregnancy (approximately 6000 binding sites per cell), declines slightly on Day 5 (approximately 4000 binding sites per cell), and then increases progressively during the remainder of pregnancy to attain its highest value on Day 22 (26,000 binding sites per cell). Nuclear receptor concentration is very low on Day 3 (1200 binding sites per cell), increases slightly on Day 5 (1900 binding sites per cell), decreases on Day 6, and then increases again to attain a plateau between Days 9 and 15 (approximately 2600 binding sites per cell). Thereafter, its concentration begins to decrease rapidly. On Day 22, the mean concentration is very low (700 binding sites per cell); in some animals (probably on the verge of parturition), no nuclear receptor can be detected.