{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:42:14Z","timestamp":1793130134979,"version":"4.5.0"},"reference-count":229,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Alterations in the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism\u2019s response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GRs) play a role in fertility, reproduction, placental function, and foetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress-induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by suppressing the hypothalamic\u2013pituitary\u2013gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother\u2019s exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the foetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GR\u03b1 and GR\u03b2, and GR\u03b3 and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in humans, guinea pigs, sheep, rats, and mice, indicating they are conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This comprehensive review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in the GR and glucocorticoid signalling during pregnancy. To generate this overview, an extensive non-systematic literature search was conducted across multiple databases, including PubMed, Web of Science, and Google Scholar, with a focus on original research articles, meta-analyses, and previous review papers addressing the subject. This review integrates the current understanding of GR variants and their roles in glucocorticoid signalling, reproduction, placental function, and foetal growth.<\/jats:p>","DOI":"10.3390\/biology12081104","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:08:59Z","timestamp":1691575739000},"page":"1104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Glucocorticoids and Their Receptor Isoforms: Roles in Female Reproduction, Pregnancy, and Foetal Development"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-4188","authenticated-orcid":false,"given":"Sreeparna","family":"Bhaumik","sequence":"first","affiliation":[{"name":"Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane 4067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Lockett","sequence":"additional","affiliation":[{"name":"Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane 4067, Australia"},{"name":"Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Metro South Health, Brisbane 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2675-8149","authenticated-orcid":false,"given":"James","family":"Cuffe","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane 4067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-6748","authenticated-orcid":false,"given":"Vicki L.","family":"Clifton","sequence":"additional","affiliation":[{"name":"Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane 4067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1074\/jbc.R110.179325","article-title":"Cellular Processing of the Glucocorticoid Receptor Gene and Protein: New Mechanisms for Generating Tissue-specific Actions of Glucocorticoids","volume":"286","author":"Oakley","year":"2011","journal-title":"J. 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