Treatment with Raloxifene Induces the Expression of Kisspeptin, Insulin, and Androgen Receptors in Bones of Castrated Adult Female Rats.

Abstract

Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1 , KISS1R , AR and INSR , by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R , INSR and AR showed higher expression in the G3 group ( p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.