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

Nonfunctioning tumors (NFTs) of the anterior pituitary often express elevated levels of the glycoprotein hormone α-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 α-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 TRβ1 and TRβ2 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 TRα1 and α2 messenger ribonucleic acids. We suggest that reduced expression of TRs and ER may account for inappropriate expression of the glycoprotein hormoneα -subunit gene in some NFTs and may contribute to uncontrolled tumor growth.