Correlation between LH and estrogen receptor turnover in pituitary and hypothalamus of castrate rats following estrogen agonists and antagonists.
A series of studies was undertaken to correlate the short-term dynamics of LH secretion and depletion-replenishment patterns of estrogen receptors (ER) in hypothalamic and pituitary cytosols of ovariectomized rats. Animals castrated for 2 weeks were administered various test compounds and analyzed at 1, 3, 5, 10 and 15 h post-treatment. A single injection of 10 micrograms 17 beta-estradiol (E2) to ovariectomized rats elicited a rapid depletion of ER in both pituitary and hypothalamus and a dramatic, though delayed, fall in serum LH. ER replenishment occurred in both tissues through 15 h and LH recovered in a similar manner. When cycloheximide was administered along with E2, ER replenishment was completely inhibited in both tissues; serum LH fell and failed to recover. Actinomycin D injected with E2 blocked replenishment in pituitary but not hypothalamus; serum LH recovered in parallel with the hypothalamic ER pattern. 17 alpha-E2 elicited only slight changes in ER and LH was suppressed 10-20% through 15 h. CI-628 caused a near total depletion of pituitary ER with no subsequent replenishment, whereas hypothalamic ER content was virtually unaltered; serum LH was suppressed and later recovered. Orchidectomized rats given 5 micrograms E2 demonstrated a less complete ER depletion in hypothalamus, and an earlier replenishment than that seen in pituitary or hypothalamus of similarly treated ovariectomized females. Serum LH rebounded to 157% of control levels at 15 h. The results indicate that the acute feedback suppression of LH by exposure to estrogens correlates with binding to ER and nuclear translocation. Replenishment and/or retention of cytoplasmic ER in hypothalamus appears to be required for full resumption of LH secretion, following acute suppression.
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D009594:Nitromifene / Q000494:pharmacology; D009919:Orchiectomy; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D003609:Dactinomycin; D004958:Estradiol; D009594:Nitromifene; D007986:Luteinizing Hormone; D003513:Cycloheximide