Delayed age-associated decrease in growth hormone pulsatile secretion and increased orexigenic peptide expression in the Lou C/JaLL rat.
Since modifications in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis and/or caloric restriction are involved in the ageing process, GH secretory profiles, total IGF-1, ghrelin, and leptin plasma levels and expression of genes implicated in somatotrope axis and food intake regulation in hypothalamus and pituitary were compared in 3-, 12-, and 24-month-old male Lou C/Jall rats and their parent strain, the Wistar rats. The Lou C/Jall strain may appear as a healthy ageing model, since it does not become obese with age and maintains its caloric intake at 2 years of age. The GH pulsatile secretion decreased from 3 months in Wistar, but only after 12 months in Lou C/Jall rats. The IGF-1 levels were lower in Lou C/Jall rats and decreased more steeply with ageing as compared with Wistar rats. The total ghrelin levels were higher in young Lou C/Jall rats than in Wistar rats, but increased similarly with age in both strains. The leptin concentrations increased with ageing only in Wistar rats. By semiquantitative reverse-transcription polymerase chain reaction, pituitary GH secretagogue receptors and GH mRNA levels were more abundant in Lou C/Jall rats, and the latter decreased with ageing in Wistar rats only. Hypothalamic growth-hormone-releasing hormone and GH secretagogue receptor mRNA levels were similar in both strains and transiently increased only in middle-aged Wistar rats. Agouti-related peptide, neuropeptide Y, and orexin mRNA levels were more abundant in the Lou C/Jall rat hypothalamus, and the two former tended to further increase with age only in this strain. Conversely, the hypothalamic pro-opiomelanocortin mRNA levels were higher in old Wistar rats. In conclusion, ageing in Lou C/Jall rats is associated with a delayed decrease in pulsatile GH secretion in the presence of a lower IGF-1 tone and an increase in the expression of orexigenic neuropeptides in the hypothalamus.
Kappeler
Laurent
L
INSERM U549, IFR Broca-Ste-Anne, Université Paris 5, Paris, France.
Zizzari
Philippe
P
Alliot
Josette
J
Epelbaum
Jacques
J
Bluet-Pajot
Marie-Thérèse
MT
D000375:Aging; D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight; D004435:Eating; D015870:Gene Expression; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000068797:Orexins; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood; D010902:Pituitary Gland / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054369:Agouti-Related Protein; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; D036361:Peptide Hormones; D012333:RNA, Messenger; C412618:agouti-related peptide, (Yc(CRFFNAFC)Y); D011333:Pro-Opiomelanocortin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone