Estrogen receptor binding in regions of the rat hypothalamus and preoptic area after inhibition of dopamine-beta-hydroxylase.
Previous studies have shown that administration of diethyldithiocarbamate (DDC), a dopamine-beta-hydroxylase inhibitor, results in a decreased concentration of estrogen receptors measured in the rodent hypothalamus and preoptic area. To determine if this modulation of receptor content is region-specific, in vitro estrogen binding assays were performed on cytosol and cell nuclear extracts of microdissected brain regions from female rats treated with DDC. For cytosol binding comparisons, ovariectomized (OVX) rats were treated with 550 mg DDC/kg b. wt. or the saline vehicle 12 h before sacrifice. For cell nuclear binding comparisons, OVX rats received a maximal dose of estradiol 12 h after DDC or saline treatment and 1 h before sacrifice. No region-specific decreases in estrogen binding were observed in either cytosol or nuclear extracts. To further examine possible regional specificity, quantitative autoradiographic analysis of the in vivo hypothalamic uptake of an iodinated analog of estradiol, 11 beta-methoxy-16 alpha-[125I]iodoestradiol (MIE2), in OVX rats treated with DDC was conducted. Animals received a saturating dose of [125I]MIE2 12 h after DDC or saline treatment and 1 h before sacrifice. DDC treatment resulted in higher background levels of radioactivity and a trend toward higher uptake levels in all brain regions, but with no evidence of marked regional specific effects in any area of the brain. In tissue uptake studies, DDC treatment resulted in higher levels of radioactivity recovered from serum and neural tissues of [125I]MIE2-injected rats, suggesting that DDC slows the clearance of MIE2.(ABSTRACT TRUNCATED AT 250 WORDS)
Brown
T J
TJ
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
Blaustein
J D
JD
Hochberg
R B
RB
MacLusky
N J
NJ
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism*; D007457:Iodine Radioisotopes; D010052:Ovariectomy; D011301:Preoptic Area / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; C060160:11-methoxy-16-iodoestradiol; D004958:Estradiol; D004299:Dopamine beta-Hydroxylase