Analysis of thyrotropin-releasing hormone-signaling components in pituitary adenomas of patients with acromegaly

In many acromegalic patients the paradoxical release of GH in response to T RH has been well documented, but the mechanisms underlying this phenomenon are not understood. It has been suggested that aberrant GH secretion may re sult from TRH endogenously synthesized by the adenoma. In 32 adenomas from acromegalic patients, TRH-like immunoreactivity (TRH-LI) was measured using 2 well characterized antisera. TRH-LI was not detectable in 10 samples, an d in 19 samples, TRH-LI was measured only by the less specific antibody. Wi th the TRH-specific antibody, TRH-LI was identified only in 3 samples, 2 of which contained exceedingly high concentrations (40 and 96 pg/mg tissue). In the latter 2 samples, prepro-TRH messenger ribonucleic acid was identifi ed by Northern blot analysis, but not in the control tissue sample of a pat ient without pituitary disease and also not in the other adenomas analyzed by this technique. Transcripts of the TRH receptor were almost undetectable in all adenomas analyzed. For the TRH-degrading ectoenzyme, a potential re gulator of TRH signals at adenohypophyseal target sites, transcripts were s ignificantly expressed only in the TRH-producing adenomas. We conclude that the TRH-signaling elements examined are, in general, not directly involved in the mechanisms causing paradoxical GH secretion in acromegalic patients .