Modulating Effect of the Leptin Fragment 116–122 on Testicular Steroidogenesis in Male Rats

A. A. Bakhtyukov; Бахтюков А. А.; I. A. Lebedev; Лебедев И. А.; В. V. S. Kuznetsova; Кузнецова В. С.; K. V. Derkach; Деркач К. В.; A. O. Shpakov; Шпаков А. О.

doi:10.31857/S0869813923050023

Modulating Effect of the Leptin Fragment 116–122 on Testicular Steroidogenesis in Male Rats

Authors: Bakhtyukov A.A.¹, Lebedev I.A.¹, Kuznetsova В.V.¹, Derkach K.V.¹, Shpakov A.O.¹
Affiliations:
1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences
Issue: Vol 109, No 5 (2023)
Pages: 689-700
Section: EXPERIMENTAL ARTICLES
URL: https://ruspoj.com/0869-8139/article/view/651572
DOI: https://doi.org/10.31857/S0869813923050023
EDN: https://elibrary.ru/XQFQGU
ID: 651572

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Abstract

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 acting on GnRH-secreting neurons and modulates testicular steroidogenic function by binding to leptin receptors in Leydig cells. A leptin fragment 116–122 (LF) including the main receptor-binding determinants of this adipokine, normalizes metabolic parameters in animals with diet-induced obesity. However, its ability to influence the steroidogenic function of the testes, including through interaction with GnRH neurons of the hypothalamus, has not been studied. The aim of this work was to study the effects of a single and three-day intranasal administration of LF (200 μg/rat) on the blood testosterone level and the expression of steroidogenic genes in the testes in mature male Wistar rats. To evaluate the effect of LF on testicular steroidogenesis upon stimulation with human chorionic gonadotropin (hCG, 15 IU/rat, s/c), a stimulator of testosterone synthesis and an antagonist of the GnRH receptor cetrorelix (75 μg/kg, s.c.) an inhibitor of testicular steroidogenesis. It has been shown that LF increases the level of testosterone in the blood after a single injection, and after a three-day administration it enhances the steroidogenic effect of hCG. LF and hCG increased the expression of the Star gene encoding the key regulatory protein of steroidogenesis StAR. Administration of cetrorelix reduced testosterone levels and Star expression, and compensatory increased expression of the luteinizing hormone receptor gene. The potentiating effect of LF on hCG-induced stimulation of testosterone levels and Star expression was not detected under conditions of GnRH antagonist treatment. Thus, LF is capable of stimulating steroidogenesis in rat testis by itself and potentiating the steroidogenic effects of hCG. Since its effects are suppressed in the presence of a GnRH antagonist, there is reason to assume that the effect of LF is realized through stimulation of hypothalamic GnRH neurons.

Keywords

leptin fragment, steroidogenesis, testosterone, GnRH receptor antagonist, luteinizing hormone receptor, human chorionic gonadotropin

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