Effects of long-term dietary interventions on pituitary growth hormone-releasing hormone receptor in aging rats and potential mechanisms of action.
Long-term moderate caloric restriction (LTMCR) is a powerful intervention to delay age-related health deterioration. In this study, the effects of 40% caloric restriction (CR), implemented at 8 months with or without protein restriction, and 40% dietary protein restriction alone, implemented at 2 months, were examined on pituitary growth hormone-releasing hormone receptor (GHRH-R) and GHRH sensitivity in 12-20-month-old male Sprague Dawley rats. An increase of the 4-kb GHRH-R mRNA transcript and 4 kb/2.5 kb ratio, the blunting of high affinity GHRH binding sites and a decrease in GHRH-induced cAMP production were observed in old rats. Only 40% CR maintained youthful levels of GHRH-R transcripts and GHRH binding parameters as well as maximal GHRH-induced cAMP production. Moreover, the GHRH-induced capacity of somatotrophs to synthesize/repair DNA in vitro, in the presence of moderate glucotoxic stress (12 mM d-glucose), was maintained in old CR rats. Among the hormonal and metabolic regulators of GHRH-R that were modified by LTMCR, glucose, free fatty acids and glucocorticoids represent promising candidates for future investigation. A better understanding of the molecular and cellular mechanisms by which they regulate the pituitary GHRH-R should help define strategies to mimic the beneficial effects of LTMCR by less demanding interventions.
Bédard
Karine
K
Laboratory of Neuroendocrinology of Aging, Centre hospitalier de l'Université de Montréal Research Center (CRCHUM), Montreal, QC, Canada H1W4A4.
Robinette
Karin
K
Ferland
Guylaine
G
Gaudreau
Pierrette
P
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001686:Biological Phenomena; D031204:Caloric Restriction; D005230:Fatty Acids, Nonesterified; D005247:Feeding Behavior / Q000187:drug effects; D005947:Glucose; D006128:Growth / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D052683:Somatotrophs / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor; D005947:Glucose