Leptin Fragment 116–122 Modulates Testicular Steroidogenesis in Male Rats.

The adipokine leptin plays an important role in the regulation of the reproductive system. It stimulates the activity of the hypothalamic–pituitary–gonadal axis by indirectly affecting gonadoliberin (GnRH)-secreting neurons and modulates testicular steroidogenesis via binding to leptin receptors in Leydig cells. The leptin fragment (LF) 116–122, which includes the main receptor-binding determinants of this adipokine, normalizes metabolic parameters in animals with a diet-induced obesity. However, its ability to influence the testicular steroidogenic function, including through interaction with hypothalamic GnRH neurons, has not been studied. The aim of this work was to study the effects of a single and 3-day intranasal LF administration (200 µg/rat) on blood testosterone levels and expression of steroidogenic genes in the testes of mature male Wistar rats, as well as to evaluate the steroidogenic activity of LF upon testosterone synthesis stimulation by human chorionic gonadotropin (hCG, 15 IU/rat, s.c.) and inhibition by the GnRH receptor antagonist Cetrorelix (75 µg/kg, s.c.). It was shown that a single LF administration increases blood testosterone levels, while a 3-day administration enhances the steroidogenic effect of hCG. LF and hCG increased the expression of the Star gene that encodes the key regulatory protein of steroidogenesis StAR. Cetrorelix administration reduced blood testosterone levels and Star expression, while compensatory increasing gene expression of the luteinizing hormone receptor. The potentiating effect of LF on hCG-induced stimulation of testosterone synthesis and Star expression was not detected after Cetrorelix treatment. Thus, LF is able to stimulate testicular steroidogenesis in rats by itself and potentiate the steroidogenic effects of hCG. Since its effects are suppressed in the presence of a GnRH antagonist, there are grounds to assume that they are implemented via stimulation of hypothalamic GnRH neurons. [ABSTRACT FROM AUTHOR]