Gene expression study of thyrotropin releasing hormone (TRH) receptor using RT-PCR: relationship to clinical and immunohistochemical phenotypes in a series of human pituitary adenomas.

Thyrotropin releasing hormone receptor 1 (TRHR1) and 2 (TRHR2) mRNAs were examined using reverse transcription polymerase chain reaction (RT-PCR). These data were then correlated with endocrinological and histological characteristics in 65 human pituitary adenomas including one non tumorous pituitary gland, to clarify the role of TRHR1 and 2 gene expression in human pituitary adenomas, especially as it relates to the paradoxical stimulatory effects of TRH found in pituitary adenomas. TRHR mRNA was not identified in four ACTH cell adenomas, whereas TRHR mRNA expression was found in 12/23 acromegaly specimens, 7/8 prolactinomas, 3/3 TSH cell adenomas, and 22/27 clinically nonfunctioning adenomas. Specimens obtained from patients expressing the TRHR gene were found to express TRHR1 and TRHR2 or TRHR1 alone, whereas no cases were identified in which TRHR2 alone was expressed. In examining the relationship between GH, PRL, TSH, or gonadotropin subunit response to TRH administration and TRHR gene expression, TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without paradoxical GH response to TRH (non-responder), whereas TRHR genes were shown to be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH (responders) (chi2 = 11.73, p = 0.0009). However, there was no significant correlation between TRHR gene expression and responsiveness to PRL or gonadotropins to TRH administration in PRL cell adenomas (chi2 = 0.16, p = 0.87) or gonadotroph cell adenomas (chi2 = 0.0006, p = 1), respectively. We concluded that the existence of the TRH receptor in adenoma cells plays an important role in the paradoxical GH response to TRH administration in GH cell adenomas. It should be noted that the PRL response to TRH in prolactinoma or an abnormal response of gonadotropin and/or its subunits to TRH in gonadotroph cell adenomas is considered to be due to a mechanism other than direct TRH action in adenoma cells. However, further studies are required to elucidate the role of TRHR2 in pituitary adenomas.