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CC BY 4.0 · Rev Bras Ortop (Sao Paulo) 2024; 59(02): e228-e234
DOI: 10.1055/s-0044-1779319
Artigo Original
Doença Osteometabólica

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

Article in several languages: português | English
Fernanda Lopes de Freitas Condi 
1   Departamento de Ortopedia, Santa Casa de Maringá, Maringá, PR, Brasil
,
Luiz Fernando Portugal Fuchs 
2   Departamento de Ginecologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Katia Candido Carvalho 
3   Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brasil
,
Edmund Chada Baracat 
3   Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brasil
› Author Affiliations Financial Support The present work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo(Fapesp; process no. 2007/54049-0) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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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.

Keywords

raloxifene hydrochloride - estrogens - genistein - kisspeptins - osteoporosis

* Work developed at the Laboratory of Structural and Molecular Gynecology (LIM 58), Discipline of Gynecology, Department of Obstetrics and Gynecology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.




Publication History

Received: 18 August 2022

Accepted: 26 June 2023

Article published online:
10 April 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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