Orexin-A regulates growth hormone-releasing hormone mRNA content in a nucleus-specific manner and somatostatin mRNA content in a growth hormone-dependent fashion in the rat hypothalamus.
The orexins or hypocretins are two neuropeptides involved in the regulation of diverse biological processes such as feeding, sleep and neuroendocrine function. Recent findings suggest a possible functional interaction between orexins, somatostatin and growth hormone-releasing hormone (GHRH) in the rat hypothalamus. In order to understand the possible functional linkage between orexins and these neuropeptides, we determined the effects of intracerebroventricular orexin-A administration on hypothalamic somatostatin and GHRH mRNA levels. Furthermore, we examined whether growth hormone (GH) mediates these interactions by using two animal models that showed GH deficiency: hypophysectomized rats and dwarf Lewis rats. Using in situ hybridization, our data showed that GHRH mRNA levels in the paraventricular nucleus of the hypothalamus are decreased after orexin-A treatment, without changes in the arcuate nucleus of the hypothalamus. On the other hand, orexin-A treatment induces a GH-dependent stimulatory effect on somatostatin mRNA content in the periventricular nucleus of the hypothalamus. Finally, we demonstrated, for the first time, that hypophysectomized rats and dwarf Lewis rats, two classical models of GH deficiency with alterations in sleep patterns, showed a marked reduction in the GHRH mRNA levels in the paraventricular nucleus of the hypothalamus. These data improve our understanding of the interactions among the different systems involved in the control and pathophysiology of food intake, sleep and GH secretion.
López
Miguel
M
Department of Physiology School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Seoane
Luisa María
LM
Tovar
Sulay
S
Nogueiras
Rubén
R
Diéguez
Carlos
C
Señarís
Rosa
R
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000008:administration & dosage*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage*; D000068797:Orexins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone