{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:18:34Z","timestamp":1747196314311,"version":"3.40.5"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In humans, the pituitary gland is covered by a fibrous capsule and is considered a continuation of the meningeal sheath. However, in rodents some studies concluded that only the <jats:italic>pars tuberalis<\/jats:italic> (PT) and <jats:italic>pars nervosa<\/jats:italic> (PN) are enwrapped by the pia mater, while others showed that the whole gland is covered by this sheath. At PT the median eminence subarachnoid drains cerebrospinal fluid (CSF) to its cisternal system representing a pathway to the hypothalamus. In the present study we examined the rat pituitary capsule to elucidate its configuration, its physical interaction with the pituitary border and its relationship with the CSF. Furthermore, we also revisited the histology of the pituitary cleft and looked whether CSF drained in it. To answer such questions, we used scanning and transmission electron microscopy, intracerebroventricular infusion of Evan\u00b4s blue, fluorescent beads, and sodium fluorescein. The latter was measured in the <jats:italic>pars distalis<\/jats:italic> (PD) and various intracranial tissues. We found a pituitary capsule resembling leptomeninges, thick at the dorsal side of the <jats:italic>pars intermedia<\/jats:italic> (PI) and PD, thicker at the level of PI in contiguity with the PN and thinner at the rostro-ventral side as a thin membrane of fibroblast-like cells embedded in a fibrous layer. The capsule has abundant capillaries on all sides. Our results showed that the CSFs bathe between the capsule and the surface of the whole gland, and ciliate cells are present in the pituitary border. Our data suggest that the pituitary gland intercommunicates with the central nervous system (CNS) through the CSF.<\/jats:p>","DOI":"10.1371\/journal.pone.0286399","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T17:27:28Z","timestamp":1685122048000},"page":"e0286399","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the rat pituitary capsule: Evidence that the cerebrospinal fluid filled the pituitary cleft and the inner side of the capsule"],"prefix":"10.1371","volume":"18","author":[{"given":"Edgar Giovanhi","family":"G\u00f3mez-Dom\u00ednguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9691-8435","authenticated-orcid":true,"given":"C\u00e9sar Gabriel","family":"Toriz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirenia","family":"Gonz\u00e1lez-Pozos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Gonz\u00e1lez-del-Pliego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsa Liliana","family":"Aguirre-Ben\u00edtez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-7922","authenticated-orcid":true,"given":"Armando","family":"P\u00e9rez-Torres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-5316","authenticated-orcid":true,"given":"Yazmin Monserrat","family":"Flores-Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Solano-Agama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Rodr\u00edguez-Mata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Garc\u00eda-God\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Mart\u00ednez-Fong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2037-0618","authenticated-orcid":true,"given":"Mar\u00eda Eugenia","family":"Mendoza-Garrido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"pone.0286399.ref001","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0006-8993(82)90949-0","article-title":"Meningeal relations of the rat hypothalamo-hypophyseal system. 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Ciric","year":"1977","journal-title":"J Neurosurg"},{"issue":"3 Suppl","key":"pone.0286399.ref003","first-page":"ons1","article-title":"Membranous layers of the pituitary gland: histological anatomic study and related clinical issues.","volume":"64","author":"Q Songtao","year":"2009","journal-title":"Neurosurgery."},{"key":"pone.0286399.ref004","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/BF00214248","article-title":"Access and distribution of exogenous substances in the intercellular clefts of the rat adenohypophysis","volume":"236","author":"B Krisch","year":"1984","journal-title":"Cell Tissue Res"},{"key":"pone.0286399.ref005","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s002219900289","article-title":"A second look at the barriers of the medial basal hypothalamus","volume":"132","author":"B Peruzzo","year":"2000","journal-title":"Exp Brain Res"},{"key":"pone.0286399.ref006","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.peptides.2010.01.003","article-title":"The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: The former opens to the portal blood and the latter to the cerebrospinal fluid","volume":"31","author":"EM Rodr\u00edguez","year":"2010","journal-title":"Peptides"},{"key":"pone.0286399.ref007","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF00210349","article-title":"Intercellular channels in the pars tuberalis of the rat hypophysis and their relationship to the subarachnoid space","volume":"218","author":"LI Aguado","year":"1981","journal-title":"Cell Tissue Res"},{"key":"pone.0286399.ref008","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00441-009-0885-8","article-title":"Cell organization of the rat pars tuberalis. 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A light- and electron-microscopic study","volume":"257","author":"DN Angelov","year":"1989","journal-title":"Cell Tissue Res"},{"key":"pone.0286399.ref019","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s11060-010-0247-0","article-title":"The pseudocapsule surrounding a pituitary adenoma and its clinical significance","volume":"101","author":"X Qu","year":"2011","journal-title":"J Neurooncol"},{"key":"pone.0286399.ref020","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tice.2013.10.001","article-title":"Intercellular communications within the rat anterior pituitary. XVI: Postnatal changes of distribution of S-100 protein positive cells, connexin 43 and LH-RH positive sites in the pars tuberalis of the rat pituitary gland. 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A dissection\/scanning electron microscopy of vascular casts","volume":"50","author":"T Murakami","year":"1987","journal-title":"Arch Histol Jap"},{"key":"pone.0286399.ref025","doi-asserted-by":"crossref","first-page":"703944","DOI":"10.3389\/fncel.2021.703944","article-title":"Living on the edge of the CNS: Meninges cell diversity in health and disease","volume":"15","author":"J Derk","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"pone.0286399.ref026","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1679\/aohc.50.393","article-title":"Light and electron microscopical studies on the appearance of a marginal layer and colloid in the pituitary cleft in young rats.","volume":"50","author":"T Ishii","year":"1987","journal-title":"Arch Histol Jap"},{"key":"pone.0286399.ref027","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1267\/ahc.11031","article-title":"Immunohistochemical localization of the water channels AQP4 and AQP5 in the rat pituitary gland","volume":"44","author":"T Matsuzaki","year":"2011","journal-title":"Acta Histochem Cytochem"},{"key":"pone.0286399.ref028","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00795-016-0148-1","article-title":"Expression and localization of forkhead box protein FOXJ1 in S100\u03b2-positive multiciliated cells of the rat pituitary.","volume":"50","author":"T Nakakura","year":"2017","journal-title":"Med Mol Morphol"},{"key":"pone.0286399.ref029","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","article-title":"Physiological roles of aquaporin-4 in brain","volume":"93","author":"EA Nagelhus","year":"2013","journal-title":"Physiol Rev"},{"key":"pone.0286399.ref030","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00441-022-03614-z","article-title":"The multiciliated cells in Rathke\u00b4s cleft express CYP26A1 and respond to retinoic acid in the pituitary","volume":"388","author":"K Horiguchi","year":"2022","journal-title":"Cell Tissue Res"},{"key":"pone.0286399.ref031","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1073\/pnas.0707886105","article-title":"Robinson ICAF. SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland","volume":"105","author":"T Fauquier","year":"2008","journal-title":"PNAS"},{"key":"pone.0286399.ref032","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.tem.2012.02.004","article-title":"A tridimensional view of pituitary development and function","volume":"23","author":"P Mollard","year":"2012","journal-title":"Trends Endocrin Metab"},{"key":"pone.0286399.ref033","doi-asserted-by":"crossref","first-page":"619352","DOI":"10.3389\/fendo.2020.619352","article-title":"Functional pituitary networks in vertebrates.","volume":"11","author":"Y Santiago-Andres","year":"2021","journal-title":"Front Endocrinol"},{"key":"pone.0286399.ref034","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ygcen.2017.05.011","article-title":"Signaling pathways to and from the hypophysial pars tuberalis, an important center for the control of seasonal rhythms","volume":"258","author":"H-W Korf","year":"2018","journal-title":"Gen Comp Endocrinol"},{"key":"pone.0286399.ref035","doi-asserted-by":"crossref","first-page":"605111","DOI":"10.3389\/fendo.2020.605111","article-title":"Effects of melatonin on anterior pituitary plasticity: A comparison between mammals and teleosts.","volume":"11","author":"E Ciani","year":"2021","journal-title":"Front Endocrinol."},{"key":"pone.0286399.ref036","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1007\/s00429-014-0719-7","article-title":"Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow\u2013Robin perivascular spaces.","volume":"219","author":"RJ Reiter","year":"2014","journal-title":"Brain Struct Funct."},{"key":"pone.0286399.ref037","doi-asserted-by":"crossref","first-page":"e12680","DOI":"10.1111\/jne.12680","article-title":"A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals","volume":"31","author":"G Helfer","year":"2019","journal-title":"J Neuroendocrinol"},{"key":"pone.0286399.ref038","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/BF00307293","article-title":"Le r\u00e9seau des cellules folliculo-stellaires et les follicules de l\u00b4ad\u00e9no hypophyse du rat (Pars distalis).","volume":"129","author":"E. 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