Jahrom University of Medical Sciences Pars Journal of Medical Sciences 2717-0284 15 1 2022 12 25 Effects of abnormal levels of testosterone on hypothalamic expression of kisspeptin in male rats Effects of abnormal levels of testosterone on hypothalamic expression of kisspeptin in male rats 43 49 700353 10.29252/jmj.15.1.43 FA Mohammad Saied Salehi Homayoun Khazali Fariba Mahmoudi Mahyar Janahmadi Journal Article 2022 12 25 In males, testosterone via negative feedback mechanism regulates gonadotropin-releasing hormone (GnRH) and gonadotropin secretion. GnRH neurons do not express androgen receptor, therefore effects of testosterone must be mediated via upstream steroid sensitive neurons. Kisspeptin neurons considered as a missing link in the feedback regulation of GnRH neurons, however central effects of supraphysiological levels of testosterone are not well understood. Since kisspeptin neurons act as a main regulator of the hypothalamic GnRH neuros, the aims of the present study were to evaluate impact of abnormal levels of testosterone on kisspeptin expression in the posterior and anterior male rat hypothalamus. Three weeks following injection of different doses of testosterone undecanoate, serum testosterone concentration was measured to ensure that experimental treatments were effective to produce desired supraphysiological levels of testosterone. Finding results using qRT-PCR revealed that gonadectomy (GDX) remarkably increased kisspeptin expression in the posterior hypothalamus. However, in GDX rats treated with different levels of testosterone, kisspeptin expression in the posterior hypothalamus did not have significant difference with control. On the other hand, we found that supraphysiological levels of testosterone increased kisspeptin expression in the anterior hypothalamus compared to control. Therefore it seems that abnormal levels of testosterone affect hypothalamic kisspeptin expression differently with its physiological levels.  In males, testosterone via negative feedback mechanism regulates gonadotropin-releasing hormone (GnRH) and gonadotropin secretion. GnRH neurons do not express androgen receptor, therefore effects of testosterone must be mediated via upstream steroid sensitive neurons. Kisspeptin neurons considered as a missing link in the feedback regulation of GnRH neurons, however central effects of supraphysiological levels of testosterone are not well understood. Since kisspeptin neurons act as a main regulator of the hypothalamic GnRH neuros, the aims of the present study were to evaluate impact of abnormal levels of testosterone on kisspeptin expression in the posterior and anterior male rat hypothalamus. Three weeks following injection of different doses of testosterone undecanoate, serum testosterone concentration was measured to ensure that experimental treatments were effective to produce desired supraphysiological levels of testosterone. Finding results using qRT-PCR revealed that gonadectomy (GDX) remarkably increased kisspeptin expression in the posterior hypothalamus. However, in GDX rats treated with different levels of testosterone, kisspeptin expression in the posterior hypothalamus did not have significant difference with control. On the other hand, we found that supraphysiological levels of testosterone increased kisspeptin expression in the anterior hypothalamus compared to control. Therefore it seems that abnormal levels of testosterone affect hypothalamic kisspeptin expression differently with its physiological levels.  https://jmj.jums.ac.ir/article_700353_8749b831f7b95b8874c6f49925988f61.pdf