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While the cause of KC remains poorly understood, changes in sex hormone levels have been correlated with KC development. This study investigated circulating gonadotropin-releasing hormone (GnRH) in control and KC subjects to determine if this master hormone regulator is linked to the KC pathology. Plasma and saliva were collected from KC subjects (n = 227 and n = 274, respectively) and non-KC controls (n = 58 and n = 101, respectively), in concert with patient demographics and clinical features. GnRH levels in both plasma and saliva were significantly lower in KC subjects compared to controls. This finding was retained in plasma when subjects were stratified based on age, sex, and KC severity. Control and KC corneal fibroblasts (HKCs) stimulated with recombinant GnRH protein in vitro revealed significantly increased luteinizing hormone receptor by HKCs and reduced expression of \u03b1-smooth muscle actin with treatment suggesting that GnRH may modulate hormonal and fibrotic responses in the KC corneal stroma. Further studies are needed to reveal the role of the hypothalamic\u2013pituitary\u2013gonadal axis in the onset and progression of KC and to explore this pathway as a novel therapeutic target.<\/jats:p>","DOI":"10.3390\/cells13201704","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:50:05Z","timestamp":1729230605000},"page":"1704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Decreased Circulating Gonadotropin-Releasing Hormone Associated with Keratoconus"],"prefix":"10.3390","volume":"13","author":[{"given":"Paulina","family":"Escandon","sequence":"first","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3071-6747","authenticated-orcid":false,"given":"Alexander J.","family":"Choi","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0719-8059","authenticated-orcid":false,"given":"Steve","family":"Mabry","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Nicholas","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-5516","authenticated-orcid":false,"given":"Rebecca L.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4238-8887","authenticated-orcid":false,"given":"Liam","family":"Redden","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-8894","authenticated-orcid":false,"given":"David A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1090-5025","authenticated-orcid":false,"given":"Kamran M.","family":"Riaz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina B.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02116, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3824","authenticated-orcid":false,"given":"Dimitrios","family":"Karamichos","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, 3430 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0002-9394(86)90817-2","article-title":"A 48-year clinical and epidemiologic study of keratoconus","volume":"101","author":"Kennedy","year":"1986","journal-title":"Am. 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