Progesterone receptor in the hypothalamic cytosol of female rats.
A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D007700:Kinetics; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011980:Receptors, Progesterone / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism
D011980:Receptors, Progesterone; D011374:Progesterone; D003907:Dexamethasone; D003345:Corticosterone