Objective: Thyrotrophin-releasing hormone (TRH) paradoxically induces the release of growth hormone (GH) when injected intravenously into acromegalic patients, although the mechanism of this action is unknown at present. Several research groups have reported that the level of TRH receptor-1 (TRHR-1) mRNA expression is variable in pituitary adenomas, and does not correlate with the degree of paradoxical GH response to TRH administration in a limited number of acromegalic patients. We aimed to compare the expression levels of TRHR-1 mRNA among various types of pituitary adenoma and to clarify whether these levels correlate with the degree of pituitary hormone response to TRH.
Patients: Pituitary adenoma tissue was obtained by surgery from 14 patients with acromegaly, four with prolactinomas, nine with nonfunctioning adenomas and one with a TSH-producing adenoma.
Methods: The level of human TRHR-1 mRNA expression in each adenoma was quantified using the competitive reverse transcription polymerase chain reaction (RT-PCR) METHOD: For amplification of a TRHR-1 cDNA fragment, a sense primer was designed according to the sequence in exon 2 and an antisense primer designed according to the sequence located at the region in exon 3 that does not encode for the alternative splicing-generated short form of TRHR-1 mRNA.
Results: TRHR-1 mRNA was detected in all pituitary adenomas examined and did not correlate with their size. The mean level of TRHR-1 mRNA expression was significantly lower in GH-producing adenomas than in prolactinomas and nonfunctioning adenomas (1.4 +/- 0.4 x 10(-2) attomol/microg total RNA, 10.7 3.4 x 10(-2) attomol/microg total RNA, and 7.2 +/- 3.3 x 10(-2) attomol/g total RNA, respectively). The ratio of plasma peak GH induced by TRH administration to the basal level of plasma GH in the patients with acromegaly correlated positively with the level of TRHR-1 mRNA expression in their GH-producing adenomas (r = 0.620, P = 0.0179). The responsiveness of plasma PRL and gonadotrophin to TRH in the patients with prolactinoma and nonfunctioning pituitary adenoma did not significantly correlate with the levels of TRHR-1 mRNA expression in their pituitary adenomas, respectively.
Conclusions: The findings of the present study suggest that the level of TRHR-1 mRNA expression varies among different types of pituitary adenoma. Furthermore, in acromegaly, the responsiveness of plasma GH to TRH administration appears to at least partially depend on the level of TRHR-1 mRNA expression in the GH-producing pituitary adenoma.