| Abstrakt: |
Leptin, secreted by adipose tissue, indirectly stimulates the activity of GnRH-producing neurons in the hypothalamus and thus regulates the functional activity of the hypothalamic–pituitary–testicular (HPT) axis. Obesity is known to be accompanied by a systemic hyperleptinemia and impaired leptin transport in the central nervous system, which limits the use of full-length leptin as a drug. It was previously shown that the intranasally administered (i.n.) leptin fragment MA-[D-Leu4]-OB3 (LF) enhances the steroidogenic effect of human chorionic gonadotropin (hCG) in rats fed a standard diet. An even more urgent task is to assess its effect on testicular steroidogenesis in obesity that reduces reproductive functions in men. This work was aimed to study the ability of LF (200 µg/kg, i.n., for 3 days) to modulate the effect of hCG (10 IU/rat, s.c., once) on testicular steroidogenesis in male Wistar rats with obesity induced by a 20-week high-fat/high-carb diet (HFHCD), as well as to evaluate the impact of the GnRH receptor antagonist Cetrorelix (ANT, 75 µg/kg, s.c., for 3 days) on the effects of LF in these animals. Obese rats demonstrated reduced testicular levels of the luteinizing hormone receptor (LHR) and a compensatorily upregulated expression of the Cyp11a1 gene encoding the steroidogenic enzyme cytochrome P450scc. LF administration enhanced hCG effects on blood testosterone levels and testicular expression of the Star gene encoding the cholesterol transporter protein StAR, which suggests the ability of LF to positively modulate HPT axis activity under obesity. ANT and LF co-administration, by contrast, reduced the stimulatory effect of hCG on blood testosterone levels and testicular Star gene expression, which may be due to the testicular effects of LF. Our data indicate the ability of LF to influence different components of the male gonadal axis under conditions of diet-induced obesity. [ABSTRACT FROM AUTHOR] |
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