Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth.
In Snell (dw) and Jackson (dwJ) dwarf mice, mutations in the gene encoding Pit-1, a tissue-specific POU-domain transcription factor, lead to the absence of somatotroph, lactotroph and thyrotroph cells. Pre-somatotroph proliferation is stimulated by increased intracellular levels of cyclic AMP, normally induced by growth hormone releasing factor (GRF; refs 7-17). Here we report the cloning of mouse and rat complementary DNAs encoding a new member of the seven-transmembrane-helix, G-protein-coupled receptor family restricted to the pituitary gland, which mediates increases in intracellular cAMP and cAMP-dependent gene transcription in response to GRF. The receptor is expressed in a spatial and temporal pattern corresponding precisely to growth hormone gene expression, and neither is expressed in dw/dw mice. The pituitary hypoplasia in these mice thus appears to be due, at least in part, to the absence of GRF receptor, which is in turn due to the absence of functional Pit-1.
Lin
C
C
Eukaryotic Regulatory Biology Program, University of California, San Diego.
Lin
S C
SC
Chang
C P
CP
Rosenfeld
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004393:Dwarfism, Pituitary / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D000242:Cyclic AMP; D004247:DNA; D004268:DNA-Binding Proteins; D019204:GTP-Binding Proteins; D013007:Growth Hormone-Releasing Hormone; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat; C048250:somatotropin releasing hormone receptor