Oestrogenic effects of neonatal administration of raloxifene on hypothalamic-pituitary-gonadal axis in male and female rats.
Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.
Pinilla
L
L
Department of Physiology, Faculty of Medicine, University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain. fi1agbee@lucano.uco.es
González
L C
LC
Gaytán
F
F
Tena-Sempere
M
M
Aguilar
E
E
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000858:Anovulation / Q000139:chemically induced; D004847:Epithelial Cells; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006066:Gonads / Q000187:drug effects* / Q000502:physiology; D006966:Hyperprolactinemia / Q000139:chemically induced; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007247:Infertility, Female / Q000139:chemically induced; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects; D014626:Vaginal Smears; D015431:Weight Loss / Q000187:drug effects
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone