Introduction: Testosterone regulates the secretion of gonadotropin-releasing hormone (GnRH) and gonadotropin through a negative feedback mechanism in males. The effects of testosterone are mediated by upstream steroid-sensitive neurons because GnRH neurons do not express androgen receptors. Kisspeptin neurons have been considered the missing link in the feedback control of GnRH neurons. Moreover, the central effects of supra-physiological levels of testosterone are not well understood. The present study was therefore conducted to determine the effect of abnormal levels of testosterone on the hypothalamic expression of kisspeptin in male rats.
Material and Methods: Three weeks following a single injection of 100, 250 and 500 mg/kg body weight of testosterone undecanoate, the blood testosterone concentration was measured to ensure that the experimental treatments have been effective in creating the desired supra-physiological levels of testosterone. The relative expression of kisspeptin was evaluated in the anterior and posterior hypothalamus using qRT-PCR and compared with the kisspeptin expression in the controlled and gonadectomized (GDX) rats (n=6 in each group).
Results: Gonadectomy was found to significantly increase the kisspeptin expression in the posterior hypothalamus in the rats; however, no significant differences were observed in the kisspeptin expression in posterior hypothalamus between the control group and the GDX rats treated with different concentrations of testosterone. On the other hand, supra-physiological levels of testosterone increased the kisspeptin expression in the anterior hypothalamus compared to in the controls.
Conclusion: Different physiological concentrations caused by abnormal testosterone levels appear to differently affect hypothalamic kisspeptin neurons.