Nitric oxide modulates in vivo and in vitro growth hormone release in acromegaly

Nitric oxide (NO) has recently been shown to modulate pituitary secretion both in vivo and in vitro. The aim of this study was to investigate the effects of this chemical transmitter on spontaneous and growth-hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion in acromegalic patients, as well as from GH-secreting tumors maintained in vitro. The study was carried out in 7 acromegalic patients (46.2 +/- 2 years) and in 5 normal subjects (40.1 +/- 1.5 years). GH and prolactin (PRL) secretion were assayed during the administration of isosorbide dinitrate (ID, 5 mg, orally), an NO donor, GHRH, and ID plus GHRH. During ID, a significant (p < 0.05) increase (37%) over basal GH levels was only observed in acromegalics. There was no change in GH levels in response to GHRH or ID plus GHRH in either group. No significant change in PRL levels was observed in either group during ID, while GHRH, with or without ID, induced a slight increase in PRL levels in acromegalics only. Tumor specimens were obtained by selective transsphenoidal adenomectomy, and the cells were plated and incubated for 1, 2 and 24 h in the presence of sodium nitroprusside, a releaser of NO (SNP, 0.3 or 0.6 mM), of GHRH (10-8 M) or of both. SNP significantly (p < 0.001) increased GH levels in a dose-dependent manner (R = 0.99, p = 0.02), but was unable to modify the GH response to GHRH. In acromegalics, a significant correlation (R = 0.822, p < 0.045) and a correlation near the limit of significance (R = 0.73, NS) were observed respectively between the in vivo GH response to ID and the in vitro response to SNP at 24 h. No significant effect was observed on PRL secretion during SNP incubations, while GHRH produced a significant increase in PRL after 2 and 24 h incubation in acromegalics. These observations indicate that NO plays a stimulatory role in vivo and in vitro on GH secretion in acromegalic patients.