Normal and Growth Hormone (GH)-Secreting Adenomatous Human Pituitaries Release Somatostatin and GH-Releasing Hormone

Abstract

Neuropeptides such as vasoactive intestinal peptide, LHRH, or TRH have been found in rat pituitary tissue and could act via paracrine or autocrine actions in this tissue. In this study we investigated whether normal human pituitary tissue and GH-secreting human pituitary adenomas could release somatostatin (SRIH) and GHRH. Fragments from three human pituitaries and dispersed cells from six GH-secreting adenomas (four adenomas were studied for GHRH release and five for SRIH release) were perifused using a Krebs-Ringer culture medium, and the perifusion medium was collected every 2 min (1 mL/fraction for 5 h). GH, GHRH, and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L TRH or SRIH. Both normal pituitaries and GH-secreting pituitary adenomas released SRIH and GHRH. SRIH release commenced 90-180 min after initiation of the perifusion, at which time GH secretion had decreased significantly. TRH stimulated SRIH release from normal pituitary tissue and inhibited SRIH release from adenoma tissue. GHRH was present at the start of the perifusion, but rapidly disappeared. However, SRIH stimulated GHRH release from normal pituitary tissue, but not from adenoma tissue. Significant amounts of GHRH and SRIH were released during the experiments, suggesting their local synthesis. These results indicate that pituitary cells can release hypothalamic peptides. The liberation of these neuropeptides is regulated, and moreover, their regulation differs between normal and adenomatous pituitaries.

Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery

“…Several clinical observations have suggested that GH pulses in this disease are generated probably within the tumor, rather than from physiological input signals such as growth hormone-releasing hormone (GHRH) and somatostatin (1,3,4,19). Further evidence for the tumoral origin of pulses was obtained by others in in vitro data of adenoma tissue, which exhibits episodic GH release in the absence of hypothalamic GHRH and somatostatin (20,21). The presence of a pituitary tumor per se does not decrease the regularity of GH secretion, since we have observed normal ApEn values for plasma GH profiles in five patients with untreated prolactinomas (unpublished data).…”

Overexpression of the growth hormone-releasing hormone gene in acromegaly-associated pituitary tumors: An event associated with neoplastic progression andaggressive behavior

“…It has been proposed that GHRH may, in consort with the competing hypophysiotropic hormone somatostatin, exert some degree of local neuroendocrine control over normal pituitary function. 48,52 In calling attention to a possible role for locally generated hypothalamic hormones in the progression of somatotroph adenomas, these data provide the basis of a new paradigm from which to view the biology and pathogenesis of these neoplasms. Historically, the development and progression of pituitary tumors have been the subject of two conceptually opposing theories.…”

Paradoxical GH response to TRH during status epilepticus in man

“…Somatostatin and GHRH secretion occur, both in GH-secreting adenoma cells and in normal human pituitary cells. TRH stimulates somatostatin release from normal cells, while inhibition of somatostatin has been demonstrated after TRH in adenomatous tissue (36). These findings may be of interest in relation to paradoxical GH responses.…”