Molecular analysis of the human growth hormone secretagogue receptor

Background: Growth hormone secretagogues (GHS) are highly potent synthetic peptides which release growth hormone (GH) by activation of a growth hormon e-releasing hormone-independent signal cascade. A specific growth hormone s ecretagogue receptor (GHS-R) has been isolated, its endogenous ligand is st ill 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 de scribed, but their specific functions are unknown. Methods and Results: A specific probe for th GHS-R was cloned following rev erse transcription and PCR amplification of pituitary mRNA. A genomic human placenta library was screened for the GHS-R gene. Positive clones wee iden tified and further characterized by Southern blotting and sequencing. A gen omic clone of 18 kb in size was determined to include the coding sequence o f both GHS-R variants. Here we show that GHS-R type 1a and type 1b are enco ded by a single gene. Sequencing of th immediate 5'-flanking region suggest s a number of transcription factor binding sites, but their functional sign ificance remains to be investigated. Conclusion: A genomic clone encoding for the two known variants of the huma n GHS-R was isolated. Further studies will determine physiological relevanc e and regulation of GHS-R. This will facilitate studies of GHS as diagnosti c and therapeutic agents in GH disorders.