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Differential Regulation of Proopiomelanocortin and Pituitary-Restricted Transcription Factor (TPIT), a New Marker of Normal and Adenomatous Human Corticotrophs

Laboratoire des Interactions Cellulaires Neuro-Endocriniennes (S.V.-K., A.E., T.B.), Unité Mixte de Recherche 6544, Centre National de la Recherche Scientifique; Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie (M.G.), Université de la Méditerranée, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine Nord, 13926 Marseille, France; Laboratoire d’Anatomie Pathologique et de Neuropathologie (D.F.-B.), Department of Neurosurgery (H.D., F.G.), and Department of Endocrinology (S.V.-K., T.B.), Centre Hospitalo-Universitaire Timone, 13385 Marseille, France; and Laboratoire de Génétique Moléculaire (A.-M.P., J.D.), Institut de Recherche Clinique de Montréal, Canada

Address all correspondence and requests for reprints to: Thierry Brue, M.D., Ph.D., Hopital de la Timone, 264 rue St Pierre, 13385 Marseille Cedex 5, France. E-mail: Thierry.Brue{at}mail.ap-hm.fr.

Since the identification of the pituitary-restricted transcription factor Tpit, a novel T-box factor that is only present in mouse in the two pituitary proopiomelanocortin (POMC)-expressing lineages, no information was available on its pattern of expression in human pituitary. We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52).

TPIT expression was restricted to the nucleus of normal or adenomatous human corticotroph cells. No specific TPIT immunostaining was detectable in all prolactin (PRL)-, GH-, or gonadotropin-secreting adenomas. In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas. Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas.

TPIT is the only currently known transcription factor selectively expressed in human normal and adenomatous corticotrophs. In human and experimental models, TPIT and its target gene POMC were thus differentially regulated by glucocorticoids. Moreover, TPIT represents a new marker of POMC-expressing pituitary cells.

Abbreviations: bHLH, Basic helix-loop-helix; e, embryonic day; Pit-1, pituitary transcription factor 1, now POU1F1 in official nomenclature; POMC, proopiomelanocortin; PRL, prolactin; PROP1, prophet of Pit-1; Tpit, pituitary-restricted transcription factor; UTP, uridine triphosphate.

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