Growth hormone (GH)-releasing hormone tonically inhibits in vitro endogenous somatostatin in human GH-secreting tumors.
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.
Mouhieddine
O E
OE
INSERM U-223, CHU Pitié-Salpétrière, Paris, France.
Levy
L
L
Benlot
C
C
Peillon
F
F
Joubert
D
D
D000236:Adenoma / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology; D046508:Culture Techniques; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis; D013004:Somatostatin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D011498:Protein Precursors; D013004:Somatostatin; C028456:prosomatostatin; D013006:Growth Hormone