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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 6 1960-1967
Copyright © 1997 by The Endocrine Society

Endocrinological Oncology

Thyroid Hormone and Estrogen Receptor Expression in Normal Pituitary and Nonfunctioning Tumors of the Anterior Pituitary1

Neil J. L. Gittoes2, Christopher J. McCabe3, Julie Verhaeg, Michael C. Sheppard and Jayne A. Franklyn

Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom B15 2TH

Address all correspondence and requests for reprints to: Dr. N. J. L. Gittoes, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom B15 2TH. E-mail n.j.gittoes{at}bham.ac.uk

Nonfunctioning tumors (NFTs) of the anterior pituitary often express elevated levels of the glycoprotein hormone {alpha}-subunit, which, under normal physiological conditions, is under negative feedback control by thyroid and gonadal steroid hormones. We postulate that inappropriately elevated levels of expression of {alpha}-subunit in the face of normal levels of these target organ hormones may reflect an abnormality of thyroid hormone receptors (TRs) and/or gonadal steroid receptors in NFTs. Using immunocytochemistry and Western blotting we have examined TR and estrogen receptor (ER) protein expression in normal human anterior pituitary glands and NFTs. Pretranslational expression of these receptors was examined using semiquantitative reverse transcriptase-PCR. Expression of all TR variant and ER proteins was reduced in pituitary tumors compared with that in normal pituitaries. The expression of messenger ribonucleic acids encoding the TRß1 and TRß2 isoforms and ER was also significantly reduced in tumors compared with normal tissues, although there was no difference between tumors and normals in the level of expression of TR{alpha}1 and {alpha}2 messenger ribonucleic acids. We suggest that reduced expression of TRs and ER may account for inappropriate expression of the glycoprotein hormone {alpha}-subunit gene in some NFTs and may contribute to uncontrolled tumor growth.




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