somatostatin-28 and Adenoma

We have previously shown that the somatostatin (SRIH) precursor (pro-SRIH) and SRIH are present in the normal human pituitary, whereas mature SRIH is never detected in GH-secreting adenomas associated with high plasma GH levels, and pro-SRIH is absent in 50% of them. Considering the fact that GHRH is present and released in vitro in higher amounts from GH adenomas than from normal human pituitaries, the possibility of a negative control exerted by GHRH on pituitary SRIH was investigated. When GH-secreting adenomas were incubated for 4 h in the presence of GHRH (10(-8) mol/L), the amount of pro-SRIH, quantified after Sephadex G-50 filtration of the acetic acid extracts, was significantly decreased. The percent inhibition was negatively correlated to the amount of endogenously released GHRH measured in the control incubation medium, suggesting a local negative feedback control exerted by pituitary GHRH on pituitary SRIH. This was further demonstrated when adenomas were incubated with a GHRH antibody. Indeed, the presence of the GHRH antibody resulted in a significant increase in the content of pro-SRIH in the adenoma. Similar results were obtained for in vitro SRIH release; exogenous GHRH induced an inhibition of SRIH release from GH-secreting adenomas, and the GHRH antibody had the opposite effect. Using a perifusion system, we showed the concomitance between the increase in GH release and the decrease in SRIH release after GHRH stimulation. Together, these results show in vitro a negative control exerted by GHRH (both exogenous and locally released) on adenomatous pituitary SRIH. This further amplifies the importance of autocrine or paracrine controls in these tumors.

Topics: Adenoma; Antibodies; Culture Techniques; Growth Hormone; Humans; Pituitary Neoplasms; Protein Precursors; Somatostatin

In contrast to normal human pituitaries, GH-secreting adenomas cannot process in vivo ProSRIH whereas they do it in vitro. The existence of an endogenous factor able to inhibit ProSRIH processing in vivo was postulated and such a role was analyzed for GHRH. Results showed that when GH adenomas are incubated in vitro with GHRH 10(-8) M, their ProSRIH contents are decreased, percent inhibition being negatively correlated to the amount of endogenously released GHRH. When incubation is performed in the presence of GHRH antibody in order to block the effect of endogenous GHRH, Pro-SRIH content is increased. The same effects are observed on SRIH release: inhibition by GHRH, stimulation by GHRH antibody. Normal rabbit serum had no effect. It may therefore be concluded that the absence of ProSRIH maturation observed in adenomas in vivo may be the consequence of the GHRH release that is known to be higher from GH adenomas than from normal pituitaries.

Topics: Adenoma; Adult; Aged; Antibodies; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Protein Precursors; Somatostatin