Role of porcine endometrial estrogen sulfotransferase in progesterone mediated downregulation of estrogen receptor.
Estrogen sulfotransferase (EST) is a progesterone (Pg) induced secretory endometrial enzyme which may effect estrogen receptor levels by esterifying estradiol-17 beta (E2) to an inactive, sulfate form. The effects of this enzyme were studied using specific inhibitors of EST that do not bind to estrogen receptor (ER): 4-nitroestrone 3-methyl ether and 4-fluoroestrone 3-methyl ether. A 1 h pulse with 4 nM E2 caused ERn (i.e. E2-bound, chromatin-bound receptor) to increase 40% in incubations of proliferative gilt endometrium (no EST activity), while the same E2 treatment of secretory endometrium (high EST activity) caused no increase in ERn. ERn accumulation was completely restored in these experiments by preincubating secretory endometrium with 4 microM 4-fluoroestrone 3-methyl ether. Gilt endometrial explants cultured 7 days with 1 nM E2 plus 1 microM Pg (which induced EST activity) possessed half the ERn as explants devoid of EST activity which were cultured in E2 alone. The addition of 10 microM 4-nitroestrone 3-methyl ester to the cultures of secretory endometrium restored ERn to the levels seen in minces cultured with E2 alone. Furthermore, ovariectomized gilts injected daily with 250 micrograms E2 plus 25 mg Pg had much lower ERn (0.06 fmol/micrograms DNA) than gilts injected with E2 only (0.21 fmol/microgram DNA). ERn was restored completely by supplementing the E2 plus Pg injections with 0.5 g 4-nitroestrone 3-methyl ether administered by vaginal suppositories.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biochemistry, Wayne State University School of Medicine, Detroit, MI 48201.
D E
DE
Saunders
M M
MM
Lozon
J D
JD
Corombos
S C
SC
Brooks
D000818:Animals; D046508:Culture Techniques; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects*; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine
D011960:Receptors, Estrogen; C037796:4-nitroestrone 3-methyl ether; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D013466:Sulfurtransferases; D015238:Sulfotransferases; C020122:estrone sulfotransferase