Severity of the catabolic condition differentially modulates hypothalamic expression of growth hormone-releasing hormone in the fasted mouse: potential role of neuropeptide Y and corticotropin-releasing hormone.
To determine whether the severity of the catabolic condition differentially regulates the GH axis, male mice were either fed ad libitum or fasted for 12, 24, and 48 h. Hypothalami, pituitaries, and stomachs were collected for assessment of mRNA levels by quantitative real-time RT-PCR, and blood collected for measurement of plasma hormone and metabolite levels by commercial assay kits. Overnight (12 h) fasting resulted in a significant suppression of circulating glucose, insulin, IGF-I, and leptin levels and an increase in corticosterone, free fatty acids, and n-octanoyl ghrelin levels, and these directional changes were maintained at the 24- and 48-h time points. Fasting (24 h) also increased circulating GH levels, which was associated with an increase in pituitary mRNA levels for GHRH receptor and ghrelin receptor and a decrease in mRNA levels for somatostatin (SST) receptor (SSTR) subtypes, SSTR2, SSTR3, and SSTR5, where the changes in ghrelin receptor and SSTR expression persisted after 48 h fasting. Hypothalamic SST mRNA levels were not altered by fasting, whereas there was a transient rise in stomach SST mRNA levels 24 h after food withdrawal. In contrast, there was a biphasic effect of fasting on GHRH expression. GHRH mRNA levels were significantly elevated at 12 and 24 h but fell to approximately 50% of fed controls 48 h after food withdrawal. A sequential rise in hypothalamic neuropeptide Y (NPY) and CRH mRNA levels preceded the fall in GHRH expression, where fasting-induced changes in CRH and GHRH mRNA levels were not observed in 48-h-fasted NPY knockout mice. These observations, in light of previous reports showing both NPY and CRH can inhibit GHRH expression and GH release, suggest that these neuronal systems may work in concert to control the ultimate impact of fasting on GH axis function.
Luque
Raul M
RM
Department of Medicine, University of Illinois, Chicago, USA.
Park
Seungjoon
S
Kineman
Rhonda D
RD
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000097:blood* / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D054440:Receptors, Ghrelin; D017481:Receptors, Somatostatin / Q000235:genetics; D012720:Severity of Illness Index
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse; C103631:somatostatin receptor 3; D007334:Insulin-Like Growth Factor I; C094573:somatostatin receptor 5; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone