The research proposed is a multidisciplinary investigation of hormonal regulation of the reproductive tract in female macaques. Monoclonal antibodies to the estrogen receptor will be used as immunocytochemical reagents to examine receptor localization and dynamics both during the natural menstrual cycle and during various hormonal states induced in spayed macaques with Silastic capsules of estradiol (E2) and progesterone (P). Biochemical assays of estrogen receptor will be correlated with the immunocy chemical procedures. A microimmunoassay based on the ability of the monoclonal antibody to shift estrogen receptors on a sucrose gradient will be developed and used to detect receptors in small tissue samples. Morphometric and ultrastructural procedures will be used to evaluate hormone effects on nuclear size, cell height, percent ciliation and stromal-epithelial boundaries in the oviduct. Special attention will be paid to differences in estrogen-receptor immunocytochemistry of stromal vs epithelial cells throughout the reproductive tract. Autoradiographic and electrophoretic techniques will be used to evaluate hormonal regulation of oviductal secretion of glycoproteins. The local effects of steroids will be examined by inserting Silastic microrods directly into subcutaneous oviducatal and endometrial transplants. A sequential analysis of P antagonism of the estrogen receptor will be conducted with subcutaneous oviductal transplants. Hormonal regulation of the progesterone receptor in the macaque reproductive tract will be studied. The ontogeny of the estrogen receptor in fetal and neonatal macaque oviducts and endometria will be examined with the immunocytochemical technique. Endometriosis will be induced in cynomolgus macaques by intraperitoneal transplantation and the endometriotic foci will be examined under different hormonal conditions by immunocytochemical, microimmunoassay, morphometric, ultrastructural and autoradiographic techniques. Rhesus monkeys with naturally occurring endometriosis will be similarly examined. Estrogen receptor levels in endometriotic lesions and normal endometrium of the same animal will be compared. The results of this latter research will be directly relevant to our understanding of human endometriosis, because this disease process is essentially identical in macaques and women. The research on oviductal glycoproteins will contribute to our knowledge of the environment in which fertilization occurs in primates.
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