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

Abstract

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 neuro-intermediate 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 effect 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 infertile or in ovx rats treated with 17β-estradiol.