Role of sulfate conjugation in estrogen metabolism and activity.
There has been an increasing interest in the sulfate conjugates of estrogens as important metabolites in steroid hormone homeostasis and activity. In women estrogen sulfates have been known as major components of plasma originating from ovarian secretion and hepatic metabolism. However, only recently has the capacity to sulfurylate estrogens been demonstrated in estrogen target tissues. Porcine uterus estrogen sulfotransferase appears only after the first complete estrous cycle. Following puberty, gilt uterine sulfurylation of estrogens is extremely active during diestrus, whereas estrogen sulfotransferase is not present during estrus. This cycling of estrogen sulfurylation in porcine and human uteri can be related directly to plasma progesterone levels. Rodent and human mammary tumors are also highly active in both steroid alcohol and estrogen sulfotransferases. Unlike uterine sulfotransferases, these enzymes are apparently stimulated by factors that appear following ovariectomy. The function of estrogen sulfurylation by target tissues remains obscure. However, recent investigations have indicated that the cyclic variation in endometrial estrogen sulfurylation may control the availability of 17 beta-estradiol to the cytoplasmic receptor. This premise is supported by the continued high estrogen sulfurylation activity and low nuclear receptor levels during implantation in fertilized gilts and sows. Utilizing purified bovine adrenal sulfotransferase, the substrate and inhibitor requirements were determined for this enzymes. It was also possible to design a specific inhibitor that will block estrogen sulfurylation without interfering with the receptor binding and nuclear migration of physiological levels of 17 beta-estradiol. This inhibitor, 3-methoxy-4-nitroestrone, will help in establishing the role of uterine and mammary estrogen sulfurylation.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D004971:Estrus; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D011247:Pregnancy; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors; D013552:Swine; D013997:Time Factors; D014599:Uterus / Q000378:metabolism
D004967:Estrogens; D004958:Estradiol; D013466:Sulfurtransferases