Medial Preoptic Microimplants of the Antiestrogen, Keoxifene, Affect Luteinizing Hormone‐Releasing Hormone mRNA Levels, Median Eminence Luteinizing Hormone‐Releasing Hormone Concentrations and Luteinizing Hormone Release in Ovariectomized, Estrogen‐Treated Rats

Abstract

Abstract We examined the temporal changes in plasma luteinizing hormone (LH) levels, median eminence luteinizing hormone-releasing hormone (LHRH) concentrations and LHRH mRNA levels in estrogen-treated, ovariectomized rats with empty or antiestrogen- containing microcannulae stereotaxically implanted into the medial preoptic area. Neither treatment disrupted the negative feedback effects of estrogen on LH secretion, but antiestrogen (Keoxifene) blocked the afternoon LH surges. In rats exhibiting LH surges, median eminence LHRH concentrations were similar at 0800, 1200 and 1600 h, but they were significantly elevated by 2000 h. In contrast, no alterations in LHRH concentrations occurred in the Keoxifene-treated group. LHRH mRNA levels in control rats were significantly elevated at 1200, 1600 and 2000 h compared with 0800 h, but LHRH mRNA levels in Keoxifene-treated rats did not change significantly over the time period examined. When we compared treatment effects over time we saw that serum LH levels were significantly higher in control than Keoxifene-treated rats only at 1600 and 2000 h. Median eminence LHRH concentrations did not differ between treatment groups until 2000 h when control animals had significantly higher levels than those of Keoxifene-treated animals. LHRH mRNA levels in Keoxifene-treated rats were significantly higher than those of controls at 0800 hand significantly lower at 1600 h. No differences in LHRH mRNA levels were detected between groups at either 1200 h or 2000 h. In summary, although it was not clear on which neuronal system estrogen acted, depriving medial preoptic neurons of this steroid in systemically estrogenized rats certainly disrupted the neural mechanisms involved in surge, but not basal LH release. In addition, neither LHRH mRNA levels nor median eminence LHRH concentrations showed variations within the period studied when the estrogen-sensitive mechanisms involved in LH release were disrupted. Therefore, the changes in LHRH mRNA levels and LHRH concentrations in the median eminence seen in surging animals probably resulted from the same neural events which triggered LH release.