title: Raloxifene analog LY 117018 effects on central and peripheral beta-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 (beta-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 beta-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 17 beta-estradiol. beta-EP contents were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in beta-EP levels in the anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no changes of beta-EP content in the hypothalamus and hippocampus were found. The administration of 17 beta-estradiol or LY 117018 in ovx rats significantly increased beta-EP concentration in the anterior and neurointermediate pituitary lobe, in the hypothalamus and plasma (p < 0.01), though they did not significantly modify hippocampal beta-EP content. When LY 117018 was administered together with 17 beta-estradiol in ovx animals, a clear anti-estrogenic effect in all organs and in plasma was observed, resulting in significantly lower beta-EP content with respect to the group treated with 17 beta-estradiol alone (p < 0.01). The chronic administration of LY 117018 in fertile rats significantly decreased beta-EP content in the anterior pituitary, hippocampus and plasma (p < 0.01), 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 neuroendocrine opiatergic pathways when administered alone in ovx rats, while it exerts an anti-estrogen effect in fertile or in ovx rats treated with 17 beta-estradiol.
authors.affiliation: Department of Reproductive Medicine and Child Development, University of Pisa, Italy.
authors.forename: A R
authors.initials: AR
authors.lastname: Genazzani
authors.forename: F
authors.initials: F
authors.lastname: Bernardi
authors.forename: M
authors.initials: M
authors.lastname: Stomati
authors.forename: S
authors.initials: S
authors.lastname: Rubino
authors.forename: L
authors.initials: L
authors.lastname: Giardina
authors.forename: S
authors.initials: S
authors.lastname: Luisi
authors.forename: P
authors.initials: P
authors.lastname: Monteleone
authors.forename: A D
authors.initials: AD
authors.lastname: Genazzani
authors.forename: M
authors.initials: M
authors.lastname: Luisi
authors.forename: F
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology*; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D011759:Pyrrolidines; D013876:Thiophenes; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D001615:beta-Endorphin; C025430:LY 117018