Local production of hypothalamic trophic peptides in human pituitary tumours

Frozen sections of human pituitary adenomas were examined for growth hormone-releasing hormone (GHRH) and thyrotrophin-releasing hormone (TRH) transcripts using in situ hybridization histochemistry. Of 56 tumours examined, clusters of TRH transcript positive cells were identified in 1 of 9 prolactinoma, 1 of 22 endocrinologically inactive adenoma, 3 of 14 somatotroph and 3 of 10 corticotroph adenomas. The number of TRH transcripts in these clusters was comparable on a cell to cell basis with TRH producing cells of simultaneously hybridized rat paraventricular nucleus (PVN). Because of their scattered distribution, however, the overall amount of TRH mRNA present in TRH transcript positive tumours was much less than that in rat PVN per unit tissue weight. In contrast to TRH transcripts which did not appear to be correlated with tumour subtype, the presence of GHRH mRNA was associated both with GH gene expression (14 of 23 GH transcript positive compared to 5 of 28 GH transcript negative) and with the clinical diagnosis of acromegaly (13 of 17 biopsies compared to 4 of 10 corticotrophs and one each of 6 lactotrophs and 18 endocrinologically inactive adenomas). In a number of the GHRH transcript positive tumours, GHRH mRNA was present in a subpopulation of cells scattered throughout the adenomas in levels similar on a cell to cell basis to those found in GHRH cells of the rat arcuate nucleus. Furthermore, as the number of GHRH mRNA positive cells was high, the transcript levels on a dpm/mg tissue basis was greater than that of rat arcuate nucleus. It is possible that locally produced GHRH contributes to the formation of some somatotroph adenomas.