Clinics (Sao Paulo). 2017 August; 72(8): 510-514.

Copyright © 2017 CLINICS

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

Rodrigo Rodrigues Marcondes I * , Kátia Cândido Carvalho I , Gisele Giannocco II , Daniele Coelho Duarte I , Natália Garcia I , José Maria Soares-Junior I , Ismael Dale Cotrim Guerreiro da Silva III , Manuel Maliqueo IV , Edmund Chada Baracat I , Gustavo Arantes Rosa Maciel I *

Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR

Laboratorio de Endocrinologia Molecular e Translacional, Departamento de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR

Laboratorio de Ginecologia Molecular e Proteomica, Departamento de Ginecologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, BR

Endocrinology and Metabolism Laboratory, Department of Medicine, West Division, University of Chile, Santiago, Chile

*Corresponding authors. E-mail:

received November 3, 2016; revised January 16, 2017; accepted March 14, 2017.



Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol.


A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis.


Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor.


Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Keywords: Polycystic Ovary Syndrome, Hypothalamus, Animal Models, Kisspeptin, Testosterone

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