Induction of c-fos mRNA in the arcuate nucleus of normal and mutant growth hormone-deficient mice by a synthetic non-peptidyl growth hormone secretagogue.
We have studied by in situ hybridization histochemistry the mRNA expression of the c-fos immediate early gene in the brains of wild type and dwarf(dw/dw) and little(lit/lit) mutant mice after systemic injections of the synthetic GH secretagogues GHRP-6 and L-163,191. Both GH secretagogues induced a marked c-fos mRNA expression in the arcuate-ventromedial hypothalamus (ARC-VMH) of both control and mutant mice indicating a possible action on growth hormone releasing hormone (GHRH) neurones in the ARC-VMH. Both dw/dw and lit/lit mice showed a 5-fold elevation in GHRH mRNA expression in the ARC-VMH compared with control animals under basal conditions. Since lit/lit mice have a reduced ability to secrete GH and lack a functional GHRH receptor while dw/dw mice lack both GH and presumably GHRH receptors, the GH-secretagogue-induced c-fos mRNA in the brain of these mutants are unlikely to be mediated by an indirect action of GH or a interaction of the synthetic GH-secretagogue with the GHRH receptor.
Sirinathsinghji
D J
DJ
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Chen
H Y
HY
Hopkins
R
R
Trumbauer
M
M
Heavens
R
R
Rigby
M
M
Smith
R G
RG
van der Ploeg
L H
LH
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001345:Autoradiography; D013006:Growth Hormone / Q000172:deficiency*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone