A. A. Bakhtyukov, I. A. Lebedev, I. Yu. Morina, V. S. Kuznetsova, A. O. Shpakov
{"title":"Leptin Fragment Modulates Stimulatory Effects of Chorionic Gonadotropin on Testicular Steroidogenesis in a Rat Model of Diet-Induced Obesity","authors":"A. A. Bakhtyukov, I. A. Lebedev, I. Yu. Morina, V. S. Kuznetsova, A. O. Shpakov","doi":"10.1134/s0022093024020066","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Leptin, secreted by adipose tissue, indirectly stimulates\nthe activity of GnRH-producing neurons in the hypothalamus and thus\nregulates the functional activity of the hypothalamic–pituitary–testicular (HPT)\naxis. Obesity is known to be accompanied by a systemic hyperleptinemia\nand impaired leptin transport in the central nervous system, which\nlimits the use of full-length leptin as a drug. It was previously\nshown that the intranasally administered (i.n.) leptin fragment\nMA-[D-Leu4]-OB3 (LF) enhances the steroidogenic effect of human\nchorionic gonadotropin (hCG) in rats fed a standard diet. An even\nmore urgent task is to assess its effect on testicular steroidogenesis\nin obesity that reduces reproductive functions in men. This work\nwas aimed to study the ability of LF (200 µg/kg, i.n., for 3 days)\nto modulate the effect of hCG (10 IU/rat, s.c., once) on testicular\nsteroidogenesis in male Wistar rats with obesity induced by a 20-week\nhigh-fat/high-carb diet (HFHCD), as well as to evaluate the impact\nof the GnRH receptor antagonist Cetrorelix (ANT, 75 µg/kg, s.c.,\nfor 3 days) on the effects of LF in these animals. Obese rats demonstrated\nreduced testicular levels of the luteinizing hormone receptor (LHR)\nand a compensatorily upregulated expression of the <i>Cyp11a1</i> gene encoding the steroidogenic enzyme\ncytochrome P450scc. LF administration enhanced hCG effects on blood\ntestosterone levels and testicular expression of the <i>Star</i> gene encoding the cholesterol\ntransporter protein StAR, which suggests the ability of LF to positively\nmodulate HPT axis activity under obesity. ANT and LF co-administration, by\ncontrast, reduced the stimulatory effect of hCG on blood testosterone\nlevels and testicular <i>Star</i> gene expression,\nwhich may be due to the testicular effects of LF. Our data indicate\nthe ability of LF to influence different components of the male\ngonadal axis under conditions of diet-induced obesity.</p>","PeriodicalId":15805,"journal":{"name":"Journal of Evolutionary Biochemistry and Physiology","volume":"129 1","pages":""},"PeriodicalIF":0.6000,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Evolutionary Biochemistry and Physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/s0022093024020066","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
