VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission
Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission governs counterregulatory hormone release. Recent studies document Ghrh control of hypoglycemia-sensitive counterregulatory neurotransmitter expression in dorsomedial VMN (VMNdm) Ghrh/steroid...
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2025-03-01
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| author | Subash Sapkota Rami Shrestha Sushma Katakam Sagor C. Roy Karen P. Briski |
| author_facet | Subash Sapkota Rami Shrestha Sushma Katakam Sagor C. Roy Karen P. Briski |
| author_sort | Subash Sapkota |
| collection | DOAJ |
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Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission governs counterregulatory hormone release. Recent studies document Ghrh control of hypoglycemia-sensitive counterregulatory neurotransmitter expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1) neurons. In this study, Ghrh receptor (Ghrh-R) gene silencing was implemented in vivo to determine if VMN Ghrh-R shapes counterregulation. Intra-VMN Ghrh-R siRNA augmented corticosterone secretion in vehicle or insulin-injected male rats, but this hormone was correspondingly refractory or inhibited in eu- versus hypoglycemic females. In each sex, gene knockdown up- or down-regulated baseline glucagon and growth hormone (GH) release, but hypoglycemia reversed the direction of Ghrh-R control of each hormone. Single-cell laser catapult-microdissected VMNdm Ghrh/SF-1 neuron multiplex qPCR analysis revealed contrary VMN Ghrh-R gene-silencing effects on eu- versus hypoglycemic SF-1 mRNA levels. In both sexes, Ghrh-R siRNA up-regulated mRNAs encoding counterregulation-repressive (γ-aminobutyric acid) or -enhancing (nitric oxide) transmitter protein markers, unrelated to plasma glycemic profiles. Ghrh-R regulation of Ghrh gene transcription was absent (euglycemic) or stimulatory (hypoglycemic) in females, and receptor control of glutaminase mRNA, a marker for the counterregulatory-augmenting neurochemical glutamate, was lost in hypoglycemic males. Ghrh-R gene silencing caused uniform up-regulation of 5′-AMP-activated protein kinase alpha-2 (AMPKα2) mRNA in each sex, independent of glucose status, but caused dissimilar changes in AMPKα1 transcription in eu- versus hypoglycemic females. The outcomes provide novel evidence that VMN Ghrh-R signaling imposes glucose-dependent control of counterregulatory hormone secretion and distinctive VMNdm neuron counterregulatory transmitter marker gene profiles. Data infer that this metabolic control may involve SF-1 (both sexes)- and AMPKα1 (female)-dependent mechanisms. |
| format | Article |
| id | doaj-art-495b0419fecd458fa3573d6f16720c41 |
| institution | DOAJ |
| issn | 2837-4010 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-495b0419fecd458fa3573d6f16720c412025-08-20T03:09:08ZengAcademia.edu JournalsAcademia Biology2837-40102025-03-013110.20935/AcadBiol7623VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmissionSubash Sapkota0Rami Shrestha1Sushma Katakam2Sagor C. Roy3Karen P. Briski4School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Rm 356 Bienville Building, 1800 Bienville Drive, Monroe, LA 71201, USA.School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Rm 356 Bienville Building, 1800 Bienville Drive, Monroe, LA 71201, USA.School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Rm 356 Bienville Building, 1800 Bienville Drive, Monroe, LA 71201, USA.School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Rm 356 Bienville Building, 1800 Bienville Drive, Monroe, LA 71201, USA.School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Rm 356 Bienville Building, 1800 Bienville Drive, Monroe, LA 71201, USA. Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission governs counterregulatory hormone release. Recent studies document Ghrh control of hypoglycemia-sensitive counterregulatory neurotransmitter expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1) neurons. In this study, Ghrh receptor (Ghrh-R) gene silencing was implemented in vivo to determine if VMN Ghrh-R shapes counterregulation. Intra-VMN Ghrh-R siRNA augmented corticosterone secretion in vehicle or insulin-injected male rats, but this hormone was correspondingly refractory or inhibited in eu- versus hypoglycemic females. In each sex, gene knockdown up- or down-regulated baseline glucagon and growth hormone (GH) release, but hypoglycemia reversed the direction of Ghrh-R control of each hormone. Single-cell laser catapult-microdissected VMNdm Ghrh/SF-1 neuron multiplex qPCR analysis revealed contrary VMN Ghrh-R gene-silencing effects on eu- versus hypoglycemic SF-1 mRNA levels. In both sexes, Ghrh-R siRNA up-regulated mRNAs encoding counterregulation-repressive (γ-aminobutyric acid) or -enhancing (nitric oxide) transmitter protein markers, unrelated to plasma glycemic profiles. Ghrh-R regulation of Ghrh gene transcription was absent (euglycemic) or stimulatory (hypoglycemic) in females, and receptor control of glutaminase mRNA, a marker for the counterregulatory-augmenting neurochemical glutamate, was lost in hypoglycemic males. Ghrh-R gene silencing caused uniform up-regulation of 5′-AMP-activated protein kinase alpha-2 (AMPKα2) mRNA in each sex, independent of glucose status, but caused dissimilar changes in AMPKα1 transcription in eu- versus hypoglycemic females. The outcomes provide novel evidence that VMN Ghrh-R signaling imposes glucose-dependent control of counterregulatory hormone secretion and distinctive VMNdm neuron counterregulatory transmitter marker gene profiles. Data infer that this metabolic control may involve SF-1 (both sexes)- and AMPKα1 (female)-dependent mechanisms.https://www.academia.edu/128458845/VMN_growth_hormone_releasing_hormone_receptor_regulation_of_counterregulatory_transmission |
| spellingShingle | Subash Sapkota Rami Shrestha Sushma Katakam Sagor C. Roy Karen P. Briski VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission Academia Biology |
| title | VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission |
| title_full | VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission |
| title_fullStr | VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission |
| title_full_unstemmed | VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission |
| title_short | VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission |
| title_sort | vmn growth hormone releasing hormone receptor regulation of counterregulatory transmission |
| url | https://www.academia.edu/128458845/VMN_growth_hormone_releasing_hormone_receptor_regulation_of_counterregulatory_transmission |
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