Structure and function of the growth-hormone-releasing hormone receptor.

Growth-hormone-releasing hormone (GHRH) stimulates growth hormone (GH) secretion and GH synthesis and is also thought to cause somatotroph proliferation. Specific high-affinity binding sites for GHRH have been demonstrated on pituitary membranes using iodinated GHRH analogs. The complementary DNA encoding for the human GHRH receptor (GHRH-R) was recently cloned. The open reading frame was shown to extend 1269 bp and thus to encode a protein of 423 amino acids with a predicted molecular weight of 47 kDa. Expression is restricted to specific tissues. Analysis of the genomic structure revealed that the human GHRH-R gene spans 15 kb and consists of 13 exons. The 5'-flanking region of the human GHRH-R gene was recently characterized. Transcriptional regulation of the GHRH-R is discussed in this review. Mechanisms of signal transduction for control of GH transcription and secretion are presented. Furthermore, the role of the GHRH-R in proliferation and differentiation of the somatotrophic pituitary cell as well as in disease is examined.