Temporal effects of progesterone domination on estrogen and oxytocin receptors in hamster uterus.
The purpose of this study was to determine whether progesterone (P)-induced down regulation of estrogen receptors (Re) and oxytocin receptors (ROT) changes with the time of P exposure. Ovariectomized hamsters were given s.c. Silastic implants of estradiol (E2) and P for 4, 8 and 16 days. Cytosol and nuclear Re were measured at low temperature with the pyridoxal phosphate exchange assay, and ROT was assayed in the membrane fraction by [3H] oxytocin binding. Nuclear Re and ROT were down regulated throughout the 16-day P exposure period, but cytosol Re (and total Re) increased progressively from 4 to 16 days indicating that the down regulation of cytosol Re escapes P control with time. This conclusion was supported by P withdrawal studies in which P implants were removed for 6 or 12 h. P withdrawal resulted in equivalent recovery responses of nuclear Re and ROT after 4, 8 and 16 days of P exposure. Although cytosol Re recovery to P withdrawal occurred at 4 and 8 days, no response was obtained after 16 days of P exposure. Uterine weight increased during steroid treatment, and morphometric analysis of the P-dominated uterus revealed significant increases in the cross sectional area of the endometrium and myometrium with time of P exposure. Cytological examination of the uterus showed prominent secretory changes in the epithelial compartment on day 16 with accumulation of secretion in the uterine lumen. These results demonstrate that P can chronically down regulate nuclear Re and ROT. However, the control of cytosol Re varies with the time of P exposure, and cytosol Re levels become refractory to P domination by 16 days. The present observations indicate that the escape of cytosol Re from P control may be associated with the proliferation of one of more uterine cell populations such as glandular and luminal epithelial cells.
D000818:Animals; D006224:Cricetinae; D003600:Cytosol / Q000032:analysis; D005260:Female; D066298:In Vitro Techniques; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D018045:Receptors, Oxytocin; D014599:Uterus / Q000032:analysis* / Q000187:drug effects
D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D018045:Receptors, Oxytocin; D011374:Progesterone