BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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 humanGHS-R we studied the gene structure. Two variants, type 1a and 1b, have been described, but their specific functions are unknown. METHODS AND RESULTS: 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. CONCLUSION: A genomic clone encoding for the two known variants of the humanGHS-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.
Authors: B L Wajchenberg; B Liberman; D Giannella Neto; M Y Morozimato; M Semer; L O Bracco; L R Salgado; M Knoepfelmacher; M H Borges; A C Pinto; C E Kater; A M Lengyel Journal: Horm Res Date: 1996
Authors: A D Howard; S D Feighner; D F Cully; J P Arena; P A Liberator; C I Rosenblum; M Hamelin; D L Hreniuk; O C Palyha; J Anderson; P S Paress; C Diaz; M Chou; K K Liu; K K McKee; S S Pong; L Y Chaung; A Elbrecht; M Dashkevicz; R Heavens; M Rigby; D J Sirinathsinghji; D C Dean; D G Melillo; A A Patchett; R Nargund; P R Griffin; J A DeMartino; S K Gupta; J M Schaeffer; R G Smith; L H Van der Ploeg Journal: Science Date: 1996-08-16 Impact factor: 47.728