[Molecular analysis of the human "growth hormone secretagogue"-receptor]

Growth hormone secretagogues (GHS) are highly potent synthetic peptides which release growth hormone (GH) by activation of a growth hormone-releasing hormone-independent signal cascade. A specific growth hormone secretagogue receptor (GHS-R) has been isolated, its endogenous ligand is still unknown. It might represent another major endocrine pathway controlling GH secretion. To gain insight into the specific function of the human GHS-R we studied the gene structure. Two variants, type 1a and 1b, have been described, but their specific functions are unknown.

A specific probe for the GHS-R was cloned following reverse transcription and PCR amplification of pituitary mRNA. A genomic human placenta library was screened for the GHS-R gene. Positive clones were identified and further characterized by Southern blotting and sequencing. A genomic clone of 18 kb in size was determined to include the coding sequence of both GHS-R variants. Here we show that GHS-R type 1a and type 1b are encoded by a single gene. Sequencing of the immediate 5'-flanking region suggests a number of transcription factor binding sites, but their functional significance remains to be investigated.

A genomic clone encoding for the two known variants of the human GHS-R was isolated. Further studies will determine physiological relevance and regulation of GHS-R. This will facilitate studies of GHS as diagnostic and therapeutic agents in GH disorders.