{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:01:45Z","timestamp":1791198105813,"version":"4.1.0"},"reference-count":17,"publisher":"Bioscientifica","issue":"7","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pituitary neuroendocrine tumors (PitNETs) exhibit diverse biological behaviors, yet the metabolic determinants underlying lineage-specific characteristics remain poorly understood. This study characterized intratumoral steroid metabolite profiles in relation to transcription factor (TF)-defined lineages and radiological tumor features in 69 PitNET specimens obtained during transsphenoidal surgery between 2021 and 2023. Tumors were classified according to the WHO 2022 TF-based criteria (SF-1, PIT-1, and TPIT). Tissue concentrations of 14 steroid metabolites were quantified via liquid chromatography\u2013tandem mass spectrometry, with associations evaluated using multivariable regression and partial least squares discriminant analysis (PLS-DA). Gonadotroph tumors (n = 34) exhibited marked pregnenolone (PREG) elevation compared with other lineages (median: 104.6 vs 1.2 ng\/g, P &amp;lt; 0.001, \u03b52 = 0.38). Corticotroph tumors (n = 9) showed enrichment of glucocorticoid metabolites, particularly 11-deoxycortisol (adjusted P = 0.002, \u03b52 = 0.30), while PIT-1 tumors (n = 23) displayed intermediate levels. PLS-DA corroborated these patterns, with 11-deoxycortisol and pregnenolone emerging as the primary discriminators (68% total variance). Multivariable analysis confirmed SF-1 lineage to be independently associated with PREG levels after adjusting for clinical and radiological covariates (adjusted R2 = 0.56, P &amp;lt; 0.001). Inverse associations were observed between deoxycorticosterone\/11-deoxycortisol and tumor expansion (r = \u22120.7 and r = \u22120.4, both P &amp;lt; 0.001), and PREG correlated with cavernous sinus invasion within gonadotroph tumors (P = 0.03). During follow-up (median: 32\u201338 months), steroid profiles showed no association with clinical outcomes. TF-defined PitNET lineages exhibit distinct intratumoral steroid profiles reflecting intrinsic metabolic properties of lineage-specific cell populations, revealing a novel metabolic dimension to PitNET biology.<\/jats:p>","DOI":"10.1530\/erc-26-0154","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:13:56Z","timestamp":1782209636000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Lineage-specific steroidomic signatures in pituitary neuroendocrine tumors: pregnenolone enrichment in SF-1 lineage and associations with tumor behavior"],"prefix":"10.1530","volume":"33","author":[{"given":"Ebubekir","family":"Akpinar","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 1 , ,","place":["Istanbul, Turkey"]},{"name":"University of Health Sciences, Pituitary Disorders Application and Research Center (HATMER) 2 , ,","place":["Basaksehir, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslihan","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 3 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suat","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 1 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buruc","family":"Erkan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 1 , ,","place":["Istanbul, Turkey"]},{"name":"University of Health Sciences, Pituitary Disorders Application and Research Center (HATMER) 2 , ,","place":["Basaksehir, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Turgal","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, Ankara University 4 , ,","place":["Ankara, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdem","family":"Altan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Basaksehir Cam and Sakura City Hospital 5 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"Kocak","sequence":"additional","affiliation":[{"name":"Department of Radiology, Basaksehir Cam and Sakura City Hospital 5 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin","family":"Karatay","sequence":"additional","affiliation":[{"name":"University of Health Sciences, Pituitary Disorders Application and Research Center (HATMER) 2 , ,","place":["Basaksehir, Turkey"]},{"name":"Department of Pathology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 6 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih Mert","family":"Dogukan","sequence":"additional","affiliation":[{"name":"University of Health Sciences, Pituitary Disorders Application and Research Center (HATMER) 2 , ,","place":["Basaksehir, Turkey"]},{"name":"Department of Pathology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital 6 , ,","place":["Istanbul, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-8866","authenticated-orcid":true,"given":"Esra","family":"Hatipoglu","sequence":"additional","affiliation":[{"name":"University of Health Sciences, Pituitary Disorders Application and Research Center (HATMER) 2 , ,","place":["Basaksehir, Turkey"]},{"name":"Division of Endocrinology, Department of Internal 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