Interaction of the Novel GH Secretagogue Hexarelin with GHRH in Regulating the Secretion of GH by Cultured Human Pituitary Somatotrophinomas in vitro

The effects of the novel GH-releasing hexapeptide, Hexarelin, on the secretion of GH in cultured human pituitary somatotrophinomas was further investigated. Hexarelin (20 nmol / L) strongly stimulated GH secretion, which could be reduced by phloretin, but not by RP-cAMPS, an inhibitor of protein kinase A (PKA). (Ac-Tyr1, D-Arg 2 ) -GRF (1 - 29) -NH 2 failed t o block the effects of Hexarelin but completely abolished the stimulation of GH secretion exerted by GHRH. When added alone to somatotrophinoma cell cultures, Hexarelin had no effect on cAMP levels, but it potentiated the stimulatory effects of GHRH. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs PKC-dependently, which might be contributed to the activation of the PI transduction system. In addition, Hexarelin could interact with GHRH on the adenylyl cyclase system.

Relationship between Invasiveness of Pituitary Somatotrophinomas and Structural Abnormalities of Protein Kinase C Gene in Human

The potential role of the protein kinase C (PKC) transduction systemin controlling proliferation of human pituitary somatotrophinomas was investigat-ed. Twenty somatotrophinomas were studied using PCR and diract sequencing methods. No point mutation within the QPKC gene, previously thought to be as-sociated with invasive pituitary tumors, was found in any of the 20 somatotrophi-nomas. It is concluded that PKC trareduction system may play an important rolein controlling pituitary somatotrophinoma proliferation, but there is no correlation between invasiveness and the previously reported QPKC gene mutation.

The Role of Protein Kinase C and Its Effect on GHRH in the Regulation of Hormone Secretion by Somatotrophinomas

Summary: Phorbol ester-induced release of growth hormone (GH) and prolactin (PRL) from hu- man somatotrophic tumors was examined in vitro. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) strongly stimulated GH and PRL secretion and showed an additive effect on GH secretion if used in combination with GH releasing hormone (GHRH). In contrast, staurosporine exerted a variable inhibitory effect on GH release. There was no correlation between such effects and gsp mutations. The findings suggested that TPA doesn't act directly through cAMP signal transduction system.

Effectsof the NovelGH Secretogogue, Hexarelin on GH Se-cretion and PhosphatidylinositolHydrolysis by Hum an Pitu-itary Som atotrophinom as in CellCulture

The effects of the novel GH releasing hexapeptide, Hexarelin, on cultured human pituitary somatotrophinomas were investigated. Hexarelin (0.01 - 100 nmol / L) dose dependently stimulated GH secretion up to 4.6 fold. Maximal effects occurred with 10 nmol / L. These effects were very similar to those observed with GHRP 6. The effects of Hexarelin were reduced by phloretin, an inhibitor of protein kinase C (PKC). The rate of phosphatidylinositol (PI) hydrolysis was markedly increased by Hexarelin in a dose dependent manner. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs in a PKC dependent manner, probably via activation of the PI transduction system.