Growth hormone-releasing factor does not stimulate phosphoinositides breakdown in primary cultures of rat and human pituitary cells.
It has been reported that rat growth hormone releasing factor (rat GRF-43), similarly to the two human GRFs (GRF-40 and 44) stimulates adenylate cyclase activity in pituitary cells. Controversial findings have been presented by two different groups on the action of GRF on phosphoinositides (PI) metabolism, a phenomenon linked to Ca-- mediated intracellular mechanisms. In the work to be reported, we evaluated the accumulation of inositol phosphates induced by GRF exposure in primary cultures of rat and human pituitary cells. Addition of rat GRF-43 to rat pituitary cells at doses up to 1 microM had no effect on inositol phosphates accumulation, while already at a dose as low as 0.05 nM it increased growth hormone secretion in the incubation medium significantly. In the same cell system, TRH, a known activator of PI breakdown, significantly increased [3H]inositol phosphates. In primary cultures of human somatotrophs from acromegalic subjects as in rats, addition of hpGRF-40 and also of TRH did not elicit any modification in the accumulation of [3H]inositol phosphates. Consistent with in vivo findings, both peptides induced a significant release of GH in the medium. Our results show that the GH releasing effect of GRF does not involve the hydrolysis of phosphatidylinositol in normal rat as well as in tumoral human somatotrophs. In addition it appears that the anomalous response of TRH on adenomatous cells from acromegalic patients is differently mediated in respect to the action of the tripeptide on normal lactotrophs and thyrotrophs.
D000172:Acromegaly / Q000378:metabolism; D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D010716:Phosphatidylinositols; D013007:Growth Hormone-Releasing Hormone