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 data are available on the effect of raloxifene on neuroendocrine function. Since beta-endorphin (β-EP) is considered a marker of neuroendocrine function, the aim of the present study was to evaluate the effects of a 14 day treatment with a raloxifene analog, LY 117018, on β-EP content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary lobe, and in the plasma of fertile and ovariectomized (ovx) rats. The effect of LY 117018 in ovx rats was compared to that of 17β-estradiol. β-EP contents were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in β-EP levels in the anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no changes of β-EP content in the hypothalamus and hippocampus were found. The administration of 17β-estradiol or LY 117018 in ovx rats significantly increased β-EP concentration in the anterior and neurointermediate pituitary lobe, in the hypothalamus and plasma (p < 0.01), though they did not significantly modify hippocampal β-EP content. When LY 117018 was administered together with 17β-estradiol in ovx animals a clear anti-estrogenic affect in all organs and in plasma was observed, resulting in significantly lower β-EP content with respect to the group treated with 17β-estradiol alone (p < 0.01). The chronic administration of LY 117018 in fertile rats significantly decreased β-EP content in the anterior pituitary, hippocampus and plasma (p < 0.01), while it increased β-EP hypothalamic content and did not change β-EP content in the neurointermediate lobe. In conclusion, raloxifene analog LY 117018 has an estrogen-like action on neuroendocrine opiatergic pathways when administered alone in ovx rats, while it exerts an anti-estrogen effect in fertile or in ovx rats treated with 17β-estradiol