Chapter 6 - Intracellular GHRP Signalling

Abstract

This chapter discusses the intracellular growth hormone-releasing peptides (GHRP) signaling. The most recent development in this field has been the identification of a GHRP receptor in several animal species including man. In spite of the efficacy and relative specificity of GHRPs for the stimulation of GH release, and the existence of a specific receptor for GHRPs, no endogenous ligand has yet been identified for these synthetic peptides. The GHRP receptors identified in the human, swine, and rat pituitary have a high degree of similarity and these receptors clearly belong to a family which is different to that of the GRF receptor and can be blocked only by specific antagonists. The available data suggest that GHRP first causes the release of intracellular Ca2+ and then causes Ca2+ influx by an increase in membrane Ca2+ permeability of the cell. The latter is due to membrane depolarization most likely via action of second messengers on Ca2+ channel protein(s). GHRP-2 stimulates cAMP accumulation in ovine somatotrophs via activation of adenylyl cyclase, but this response is not seen in rat somatotrophs. This appears to be the pathway responsible for the stimulation of GH secretion by GHRP-2 in the sheep. GHRP-6 and GHRP-1 elevate cAMP levels in ovine, rat, and human somatotrophs and amplify the cAMP response to GRF in rat pituitary cells. This suggests activation of different cyclases by the different secretagogues.