Extrapituitary effects of the growth hormone-releasing hormone

Growth hormone-releasing hormone (GHRH) is a neuropeptide secreted by the hypothalamus that stimulates the synthesis and release of growth hormone (GH) in the pituitary. Accumulating evidence suggests that in addition to GHRH's neuroendocrine action, GHRH is present in several extrahypothalamic tissues and is involved in a variety of cellular processes. Its function is related to the regulation of cell proliferation and differentiation of various nonpituitary cell types. In certain cases, ectopic production of GHRH has also been implicated in carcinogenesis. The mechanisms by which GHRH affects the peripheral extrapituitary tissues remain poorly understood, but it is likely that classic neuroendocrine action as well as paracrine and autocrine pathways are involved. Some headway has been made in the identification of extrapituitary receptors for GHRH and cDNA as splice variants of these GHRH receptors found in various tumors. The fact that the nonpituitary GHRH receptors are not fully identified, however, remains the major obstacle in studying, at a more mechanistic level, the action of local GHRH. This review summarizes the information available regarding the role of GHRH in the extrapituitary tissues with emphasis on its potential therapeutic and diagnostic applications.