Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats
Neonatal L-monosodium glutamate (MSG) administration in rats induces several neuroendocrine and metabolic disruptions. Leptin, the adipocyte product, modulates several neuroendocrine systems including the hypothalamic-pituitary- gonadal (HPG) axis in mammals. The aim of the present study was to dete...
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2003
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v78_n5_p270_Giovambattista http://hdl.handle.net/20.500.12110/paper_00283835_v78_n5_p270_Giovambattista |
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paper:paper_00283835_v78_n5_p270_Giovambattista2023-06-08T14:55:05Z Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats Gonadal steroids Hypogonadism Leptin Leydig cells Monosodium glutamate Steroidogenesis Testis androstenedione chorionic gonadotropin glutamate sodium hydroxyprogesterone leptin messenger RNA testosterone animal cell animal experiment animal model animal tissue article cell function controlled study drug effect female hormone release hyperleptinemia hypogonadism in vitro study Leydig cell male neuroendocrine disease nonhuman priority journal protein expression rat spermatogenesis steroidogenesis testis testosterone release Analysis of Variance Androstenols Animals Animals, Newborn Blotting, Northern Body Weight Disease Models, Animal Dose-Response Relationship, Drug Female Follicle Stimulating Hormone Hypogonadism Leptin Leydig Cells Luteinizing Hormone Male Mice Organ Size Radioimmunoassay Rats Rats, Sprague-Dawley Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sodium Glutamate Testis Testosterone Thyroxine Neonatal L-monosodium glutamate (MSG) administration in rats induces several neuroendocrine and metabolic disruptions. Leptin, the adipocyte product, modulates several neuroendocrine systems including the hypothalamic-pituitary- gonadal (HPG) axis in mammals. The aim of the present study was to determine whether MSG-induced chronic hyperleptinemia could play any relevant role in the hypogonadism developed by male rats when examined in adulthood. We found that 120-day-old MSG male rats displayed significant hyperleptinemia, hypogonadism, and undisturbed basic testis structure and spermatogenesis. In vitro studies in purified Leydig cells from normal (CTR) and MSG-damaged rats revealed that basal and human chorionic gonadotropin (hCG)-stimulated 17-hydroxy-progesterone (17-HO-P4,) Δ4-androstenedione (Δ 4A) and testosterone (T) secretions were significantly lower in MSG than in CTR cells. Exposure to murine leptin (mleptin, 10-8 M) significantly inhibited hCG-elicited T secretion by CTR cells after 180 min incubation. While mleptin significantly inhibited hCG-stimulated Δ 4A output and the Δ4A:17-OH-P4 ratio of secretion, conversely, it failed to modify the ratio T:Δ4A release by CTR Leydig cells. Interestingly, the effects of mleptin found on CTR Leydig cells were absent in MSG Leydig cells. Finally, endogenous hyperleptinemia was associated with a significant decrease in Leydig cell expression of Ob-Rb mRNA in MSG rats. In summary, this study demonstrates that: (1) mleptin inhibited testicular steroidogenesis in CTR rats; (2) MSG-treated rats showed lower in vitro 17-OH-P4, Δ4A and T production under basal and post-hCG stimulation conditions; (3) purified Leydig cells from MSG-treated rats displayed resistance to the inhibitory action of mleptin on T release, and (4) endogenous leptin exerts a modulatory effect on Leydig cell Ob-Rb mRNA expression. The inhibitory effect of leptin on testicular function is thus abrogated in MSG-damaged rats. The testicular leptin-resistance developed by MSG rats seems to be due to early chronic exposure of Leydig cells to high leptin circulating levels, which in turn down-regulate testicular Ob-Rb expression. It remains to be determined whether the testicular dysfunction of MSG rats can be reversed after correction of hyperleptinemia or whether it is an irreversible effect of the hypothalamic lesion. Copyright © 2003 S. Karger AG, Basel. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v78_n5_p270_Giovambattista http://hdl.handle.net/20.500.12110/paper_00283835_v78_n5_p270_Giovambattista |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Gonadal steroids Hypogonadism Leptin Leydig cells Monosodium glutamate Steroidogenesis Testis androstenedione chorionic gonadotropin glutamate sodium hydroxyprogesterone leptin messenger RNA testosterone animal cell animal experiment animal model animal tissue article cell function controlled study drug effect female hormone release hyperleptinemia hypogonadism in vitro study Leydig cell male neuroendocrine disease nonhuman priority journal protein expression rat spermatogenesis steroidogenesis testis testosterone release Analysis of Variance Androstenols Animals Animals, Newborn Blotting, Northern Body Weight Disease Models, Animal Dose-Response Relationship, Drug Female Follicle Stimulating Hormone Hypogonadism Leptin Leydig Cells Luteinizing Hormone Male Mice Organ Size Radioimmunoassay Rats Rats, Sprague-Dawley Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sodium Glutamate Testis Testosterone Thyroxine |
spellingShingle |
Gonadal steroids Hypogonadism Leptin Leydig cells Monosodium glutamate Steroidogenesis Testis androstenedione chorionic gonadotropin glutamate sodium hydroxyprogesterone leptin messenger RNA testosterone animal cell animal experiment animal model animal tissue article cell function controlled study drug effect female hormone release hyperleptinemia hypogonadism in vitro study Leydig cell male neuroendocrine disease nonhuman priority journal protein expression rat spermatogenesis steroidogenesis testis testosterone release Analysis of Variance Androstenols Animals Animals, Newborn Blotting, Northern Body Weight Disease Models, Animal Dose-Response Relationship, Drug Female Follicle Stimulating Hormone Hypogonadism Leptin Leydig Cells Luteinizing Hormone Male Mice Organ Size Radioimmunoassay Rats Rats, Sprague-Dawley Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sodium Glutamate Testis Testosterone Thyroxine Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
topic_facet |
Gonadal steroids Hypogonadism Leptin Leydig cells Monosodium glutamate Steroidogenesis Testis androstenedione chorionic gonadotropin glutamate sodium hydroxyprogesterone leptin messenger RNA testosterone animal cell animal experiment animal model animal tissue article cell function controlled study drug effect female hormone release hyperleptinemia hypogonadism in vitro study Leydig cell male neuroendocrine disease nonhuman priority journal protein expression rat spermatogenesis steroidogenesis testis testosterone release Analysis of Variance Androstenols Animals Animals, Newborn Blotting, Northern Body Weight Disease Models, Animal Dose-Response Relationship, Drug Female Follicle Stimulating Hormone Hypogonadism Leptin Leydig Cells Luteinizing Hormone Male Mice Organ Size Radioimmunoassay Rats Rats, Sprague-Dawley Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sodium Glutamate Testis Testosterone Thyroxine |
description |
Neonatal L-monosodium glutamate (MSG) administration in rats induces several neuroendocrine and metabolic disruptions. Leptin, the adipocyte product, modulates several neuroendocrine systems including the hypothalamic-pituitary- gonadal (HPG) axis in mammals. The aim of the present study was to determine whether MSG-induced chronic hyperleptinemia could play any relevant role in the hypogonadism developed by male rats when examined in adulthood. We found that 120-day-old MSG male rats displayed significant hyperleptinemia, hypogonadism, and undisturbed basic testis structure and spermatogenesis. In vitro studies in purified Leydig cells from normal (CTR) and MSG-damaged rats revealed that basal and human chorionic gonadotropin (hCG)-stimulated 17-hydroxy-progesterone (17-HO-P4,) Δ4-androstenedione (Δ 4A) and testosterone (T) secretions were significantly lower in MSG than in CTR cells. Exposure to murine leptin (mleptin, 10-8 M) significantly inhibited hCG-elicited T secretion by CTR cells after 180 min incubation. While mleptin significantly inhibited hCG-stimulated Δ 4A output and the Δ4A:17-OH-P4 ratio of secretion, conversely, it failed to modify the ratio T:Δ4A release by CTR Leydig cells. Interestingly, the effects of mleptin found on CTR Leydig cells were absent in MSG Leydig cells. Finally, endogenous hyperleptinemia was associated with a significant decrease in Leydig cell expression of Ob-Rb mRNA in MSG rats. In summary, this study demonstrates that: (1) mleptin inhibited testicular steroidogenesis in CTR rats; (2) MSG-treated rats showed lower in vitro 17-OH-P4, Δ4A and T production under basal and post-hCG stimulation conditions; (3) purified Leydig cells from MSG-treated rats displayed resistance to the inhibitory action of mleptin on T release, and (4) endogenous leptin exerts a modulatory effect on Leydig cell Ob-Rb mRNA expression. The inhibitory effect of leptin on testicular function is thus abrogated in MSG-damaged rats. The testicular leptin-resistance developed by MSG rats seems to be due to early chronic exposure of Leydig cells to high leptin circulating levels, which in turn down-regulate testicular Ob-Rb expression. It remains to be determined whether the testicular dysfunction of MSG rats can be reversed after correction of hyperleptinemia or whether it is an irreversible effect of the hypothalamic lesion. Copyright © 2003 S. Karger AG, Basel. |
title |
Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
title_short |
Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
title_full |
Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
title_fullStr |
Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
title_full_unstemmed |
Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
title_sort |
modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats |
publishDate |
2003 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283835_v78_n5_p270_Giovambattista http://hdl.handle.net/20.500.12110/paper_00283835_v78_n5_p270_Giovambattista |
_version_ |
1768545962493476864 |