Immunohistochemical Expression of Retinoid X Receptor Isoforms in Human Pituitaries and Pituitary Adenomas

Retinoid X receptors (RXRs) are transcriptional factors that belong to the steroid/thyroid hormone receptor superfamily. There are 3 RXR isoforms – α, β, γ – known to bind 9-cisretinoic acid as their ligand. The expression of RXRs in human pituitary glands and pituitary adenomas has not been extensively investigated. To determine whether specific RXR isoforms may play roles in the state of differentiation of pituitary adenomas, we have investigated the immunohistochemical expression of RXRα and RXRγ in 6 nontumorous pituitaries and in 60 different pituitary adenomas using isoform-specific antibodies. In the nontumorous pituitaries, RXRα was expressed in the nuclei of almost all cells, while RXRγ was only expressed in thyrotropin (TSH) cells and in some cells positive for growth hormone (GH) and glycoprotein α-subunit (αSU) but not in luteinizing hormone (LH) β-subunit, follicle-stimulating hormone (FSH) β-subunit, prolactin (PRL) or adrenocorticotropin (ACTH) cells by double immunostaining. All 60 adenomas were RXRα positive, and 39 of 60 adenomas (65%) were positive for RXRγ. The incidence of RXRγ immunoreactivity in the different adenoma types was: 13 of 16 GH-producing adenomas (81.3%), 9 of 14 PRL-secreting adenomas (64.3%), 6 of 6 TSH-secreting adenomas (100%), 2 of 5 ACTH-secreting adenomas (40%) and 9 of 19 nonfunctioning adenomas (47.4%) including immunohistochemically gonadotropin-subunit-positive adenomas. The colocalization of RXRγ with the TSHβ subunit, GH and αSU in the same adenoma cells was frequently observed, and sometimes RXRγ was colocalized with PRL, ACTH, FSHβ or LHβ as shown by double immunostaining. We conclude that RXRα is expressed in both human pituitaries and pituitary adenomas. In contrast, RXRγ is expressed more broadly in pituitary adenomas than in normal pituitaries and thus may play a role in the differentiation-specific cell types in the human pituitary both under physiological and pathological conditions.