{"title":"Estrogen promotes fetal skeletal muscle mitochondrial distribution and ATP synthase activity important for insulin sensitivity in offspring.","authors":"Soon Ok Kim, Eugene D Albrecht, Gerald J Pepe","doi":"10.1007/s12020-024-03764-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>We previously showed that offspring delivered to baboons in which levels of estradiol (E<sub>2</sub>) were suppressed during the second half of gestation exhibit insulin resistance. Mitochondria are essential for the production of ATP as the main source of energy for intracellular metabolic pathways, and skeletal muscle of type 2 diabetics exhibit mitochondrial abnormalities. Mitochondria express estrogen receptor β and E<sub>2</sub> enhances mitochondrial function in adults. Therefore, the current study ascertained whether exposure of the fetus to E<sub>2</sub> is essential for mitochondrial development.</p><p><strong>Methods: </strong>Levels of ATP synthase and citrate synthase and the morphology of mitochondria were determined in fetal skeletal muscle obtained near term from baboons untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus E<sub>2</sub>.</p><p><strong>Results: </strong>Specific activity and amount of ATP synthase were 2-fold lower (P < 0.05) in mitochondria from skeletal muscle of E<sub>2</sub> suppressed letrozole-treated fetuses and restored to normal by treatment with letrozole plus E<sub>2</sub>. Immunocytochemistry showed that in contrast to the punctate formation of mitochondria in myocytes of untreated and letrozole plus E<sub>2</sub> treated animals, mitochondria appeared to be diffuse in myocytes of estrogen-suppressed fetuses. However, citrate synthase activity and levels of proteins that control mitochondrial fission/fusion were similar in estrogen replete and suppressed animals.</p><p><strong>Conclusion: </strong>We suggest that estrogen is essential for fetal skeletal muscle mitochondrial development and thus glucose homeostasis in adulthood.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246263/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-024-03764-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: We previously showed that offspring delivered to baboons in which levels of estradiol (E2) were suppressed during the second half of gestation exhibit insulin resistance. Mitochondria are essential for the production of ATP as the main source of energy for intracellular metabolic pathways, and skeletal muscle of type 2 diabetics exhibit mitochondrial abnormalities. Mitochondria express estrogen receptor β and E2 enhances mitochondrial function in adults. Therefore, the current study ascertained whether exposure of the fetus to E2 is essential for mitochondrial development.
Methods: Levels of ATP synthase and citrate synthase and the morphology of mitochondria were determined in fetal skeletal muscle obtained near term from baboons untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus E2.
Results: Specific activity and amount of ATP synthase were 2-fold lower (P < 0.05) in mitochondria from skeletal muscle of E2 suppressed letrozole-treated fetuses and restored to normal by treatment with letrozole plus E2. Immunocytochemistry showed that in contrast to the punctate formation of mitochondria in myocytes of untreated and letrozole plus E2 treated animals, mitochondria appeared to be diffuse in myocytes of estrogen-suppressed fetuses. However, citrate synthase activity and levels of proteins that control mitochondrial fission/fusion were similar in estrogen replete and suppressed animals.
Conclusion: We suggest that estrogen is essential for fetal skeletal muscle mitochondrial development and thus glucose homeostasis in adulthood.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
