Raloxifene analog LY 117018 effects on central and peripheral beta-endorphin

Raloxifene is a selective estrogen receptor modulator with a benzothiophene structure, that exerts an estrogen-like action on some target tissues and an anti-estrogenic action on the uterus and breasts. A limited number of da ta are available on the effect of raloxifene on neuroendocrine function. Si nce beta-endorphin (beta-EP) is considered a marker of neuroendocrine funct ion, the aim of the present study was to evaluate the effects of a 14 day t reatment with a raloxifene analog, LY 117018, on beta-EP content in the hyp othalamus, hippocampus, anterior and neurointermediate pituitary lobe, and in the plasma of fertile and ovariectomized (ovx) rats. The effect of LY 11 7018 in ovx rats was compared to that of 17 beta-estradiol. beta-EP content s were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in beta-EP levels in th e anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no c hanges of beta-EP content in the hypothalamus and hippocampus were found. T he administration of 17 beta-estradiol or LY 117018 in ovx rats significant ly increased beta-EP concentration in the anterior and neurointermediate pi tuitary lobe, in the hypothalamus and plasma (p < 0.01), though they did no t significantly modify hippocampal beta-EP content. When LY 117018 was admi nistered together with 17 beta-estradiol in ovx animals, a clear anti-estro genic effect in all organs and in plasma was observed, resulting in signifi cantly lower beta-EP content with respect to the group treated with 17 beta -estradiol alone (p < 0.01). The chronic administration of LY 117018 infertile rats significantly decrea sed P-EP content in the anterior pituitary, hippocampus and plasma (p < 0.0 1), while it increased beta-EP hypothalamic content and did not change beta -EP content in the neurointermediate lobe. In conclusion, raloxifene analog LY 117018 has an estrogen-like action On n euroendocrine opiatergic pathways when administered alone in ovx rats, whil e it exerts an anti-estrogen effect infertile or in ovx rats treated with 1 7 beta-estradiol.