Sex-dependent endozepinergic regulation of ventromedial hypothalamic nucleus glucose counter-regulatory neuron aromatase protein expression in the adult rat

IF 2.7 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of chemical neuroanatomy Pub Date : 2023-10-01 DOI:10.1016/j.jchemneu.2023.102323

A.S.M. Hasan Mahmood , Sagor C. Roy , Jérôme Leprince , Karen P. Briski

{"title":"Sex-dependent endozepinergic regulation of ventromedial hypothalamic nucleus glucose counter-regulatory neuron aromatase protein expression in the adult rat","authors":"A.S.M. Hasan Mahmood , Sagor C. Roy , Jérôme Leprince , Karen P. Briski","doi":"10.1016/j.jchemneu.2023.102323","DOIUrl":null,"url":null,"abstract":"<div>The hypothalamic brain cell types that produce estradiol from testosterone remain unclear. Aromatase inhibition affects ventromedial hypothalamic nucleus (VMN) glucose-stimulatory nitric oxide (NO) and glucose-inhibitory γ-aminobutyric acid (GABA) transmission during insulin (INS)-induced hypoglycemia (IIH). Pure GABA and NO nerve cell samples acquired by laser-catapult-microdissection from consecutive rostro-caudal segments of the VMN were analyzed by Western blot to investigate whether regional subpopulations of each cell type contain machinery for neuro-estradiol synthesis. Astrocyte endozepinergic signaling governs brain steroidogenesis. Pharmacological tools were used here to determine if the glio-peptide octadecaneuropeptide (ODN) controls aromatase expression in GABA and NO neurons during eu- and/or hypoglycemia. Intracerebroventricular administration of the ODN G-protein coupled-receptor antagonist cyclo(1−8)[DLeu5]OP (LV-1075) decreased (male) or enhanced (female) VMN GABAergic neuron aromatase expression, but increased or reduced this profile in nitrergic neurons in a region-specific manner in each sex. IIH suppressed aromatase levels in GABA neurons located in the middle segment of the male VMN or distributed throughout this nucleus in the female. This inhibitory response was altered by the ODN isoactive surrogate octapeptide (OP) in female, but was refractory to OP in male. NO neuron aromatase protein in hypoglycemic male (middle and caudal VMN) and female (rostral and caudal VMN) rats, but was normalized in OP- plus INS-treated rats of both sexes. Results provide novel evidence that VMN glucose-regulatory neurons may produce neuro-estradiol, and that the astrocyte endozepine transmitter ODN may impose sex-specific control of baseline and/or hypoglycemic patterns of aromatase expression in distinct subsets of nitrergic and GABAergic neurons in this neural structure.</div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"132 ","pages":"Article 102323"},"PeriodicalIF":2.7000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528386/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061823000935","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The hypothalamic brain cell types that produce estradiol from testosterone remain unclear. Aromatase inhibition affects ventromedial hypothalamic nucleus (VMN) glucose-stimulatory nitric oxide (NO) and glucose-inhibitory γ-aminobutyric acid (GABA) transmission during insulin (INS)-induced hypoglycemia (IIH). Pure GABA and NO nerve cell samples acquired by laser-catapult-microdissection from consecutive rostro-caudal segments of the VMN were analyzed by Western blot to investigate whether regional subpopulations of each cell type contain machinery for neuro-estradiol synthesis. Astrocyte endozepinergic signaling governs brain steroidogenesis. Pharmacological tools were used here to determine if the glio-peptide octadecaneuropeptide (ODN) controls aromatase expression in GABA and NO neurons during eu- and/or hypoglycemia. Intracerebroventricular administration of the ODN G-protein coupled-receptor antagonist cyclo₍₁₋₈₎[DLeu⁵]OP (LV-1075) decreased (male) or enhanced (female) VMN GABAergic neuron aromatase expression, but increased or reduced this profile in nitrergic neurons in a region-specific manner in each sex. IIH suppressed aromatase levels in GABA neurons located in the middle segment of the male VMN or distributed throughout this nucleus in the female. This inhibitory response was altered by the ODN isoactive surrogate octapeptide (OP) in female, but was refractory to OP in male. NO neuron aromatase protein in hypoglycemic male (middle and caudal VMN) and female (rostral and caudal VMN) rats, but was normalized in OP- plus INS-treated rats of both sexes. Results provide novel evidence that VMN glucose-regulatory neurons may produce neuro-estradiol, and that the astrocyte endozepine transmitter ODN may impose sex-specific control of baseline and/or hypoglycemic patterns of aromatase expression in distinct subsets of nitrergic and GABAergic neurons in this neural structure.

查看原文本刊更多论文

成年大鼠下丘脑腹内侧核葡萄糖反调节神经元芳香化酶蛋白表达的性别依赖性内周调节。

从睾酮中产生雌二醇的下丘脑脑细胞类型尚不清楚。在胰岛素（INS）诱导的低血糖（IIH）过程中，芳香化酶抑制影响下丘脑腹内侧核（VMN）葡萄糖刺激性一氧化氮（NO）和葡萄糖抑制性γ-氨基丁酸（GABA）的传递。通过Western印迹分析通过激光弹射器显微切割从VMN的连续头尾节段获得的纯GABA和NO神经细胞样本，以研究每种细胞类型的区域亚群是否含有神经雌二醇合成的机制。星形胶质细胞内星形胶质细胞信号支配大脑类固醇生成。药理学工具用于确定胶质肽十八碳五肽（ODN）是否在eu和/或低血糖期间控制GABA和NO神经元中芳香化酶的表达。侧脑室内施用ODN G蛋白偶联受体拮抗剂cyclo（1-8）[DLeu5]OP（LV-1075）降低（男性）或增强（女性）VMN GABA能神经元芳香化酶表达，但在每种性别中，以区域特异性的方式增加或减少了氮能神经元中的这种分布。IIH抑制了位于男性VMN中段或分布在女性整个细胞核的GABA神经元中的芳香化酶水平。这种抑制反应在雌性中被ODN等活性替代八肽（OP）改变，但在雄性中对OP是难治的。NO神经元芳香化酶蛋白在低血糖雄性（中尾VMN）和雌性（吻端和尾端VMN）大鼠中表达，但在OP加INS处理的两性大鼠中均正常化。结果提供了新的证据，表明VMN葡萄糖调节神经元可能产生神经雌二醇，星形胶质细胞内泽平递质ODN可能对该神经结构中不同亚群的氮能和GABA能神经元的芳香化酶表达的基线和/或低血糖模式施加性别特异性控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of chemical neuroanatomy 医学-神经科学

CiteScore

4.50

自引率

3.60%

发文量

审稿时长

62 days

期刊介绍： The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.