Regulation of the Pituitary Growth Hormone-Releasing Hormone Receptor in Ageing Male and Female LOU Rats: New Insights into Healthy Ageing

• Published in: Journal of neuroendocrinology Vol. 17; no. 11; pp. 691 - 700
• Main Authors: Veyrat-Durebex, C., Alliot, J., Gaudreau, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-11-2005; Blackwell Science; Wiley Subscription Services, Inc
• Subjects: Aging - metabolism; Animals; anterior pituitary; Biological and medical sciences; Blotting, Northern; Body Weight - physiology; Diet; Female; Fluo-GHRH; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; IGF-I; Insulin-Like Growth Factor I - metabolism; leptin; Leptin - blood; Male; Pituitary Gland - growth & development; Pituitary Gland - metabolism; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Neuropeptide - biosynthesis; Receptors, Neuropeptide - metabolism; Receptors, Pituitary Hormone-Regulating Hormone - biosynthesis; Receptors, Pituitary Hormone-Regulating Hormone - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; thyroxin; Thyroxine - blood; Vertebrates: endocrinology; Senescence; Endocrine gland; Rat; anterior pituitary; Somatotropin hormone; Male; Adenohypophysis; Female; Hormone releasing factor; thyroxin; Somatotropin releasing factor; Ageing; Rodentia; IGF-1; Adipokine; Insulin like growth factor 1; Hypothalamic hormone; Vertebrata; Pituitary hormone; Mammalia; Adenohypophyseal hormone; Animal; Leptin; Fluo-GHRH; Hormonal receptor
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2005.01343.x

Ageing is characterised by a decrease of somatotroph functionality, involving growth hormone‐releasing hormone receptor (GHRH‐R). The present study was conducted in LOU/C/jall (LOU) rats, a strain described as a model of healthy ageing, which is characterised by a low adiposity and long life expectancy without developing severe pathologies. Effects of age and diet (chow versus self‐selection), on levels of anterior pituitary GHRH‐R mRNA transcripts, were assessed in male and female LOU rats. The effect of age on pituitary GHRH‐R functionality was examined in the anterior pituitary of both males and females fed chow diet. Moreover, serum insulin‐like growth factor‐I (IGF‐I), T4 and leptin were measured because changes in their concentration could affect GHRH‐R expression. In the pituitary of 18‐month‐old male and female LOU/C/jall rats fed standard chow, the level of 2.5‐kb GHRH‐R mRNA transcript, coding for functional GHRH‐R, was significantly decreased. In 24‐ to 34‐month‐old males and females, it progressively returned to the level of younger animals, suggesting an enrichment of the group with survivors maintaining functional GHRH‐R. In males and females repeatedly submitted to self‐selection, this phenomenon was not observed. Studies with the GHRH‐R agonist, Fluo‐GHRH, revealed that 73% of 16–18‐month‐old male and female rats studied did not show an increase of fluorescence density characteristic of receptor‐mediated internalisation upon incubation at 37 °C. In the other 27%, the increase of fluorescence was identical to that observed in pituitaries of young rats, suggesting the presence of an optimal level of functional GHRH‐R. Serum levels of leptin, free T4 and total IGF‐I decreased more drastically in ageing males and in rats fed a self‐selection diet. A positive correlation was demonstrated between leptin and IGF‐I levels in ageing males and females fed standard chow and ageing females submitted to a self‐selection regimen. In conclusion, healthy ageing in LOU rats fed chow diet appears to be associated with a maintenance of functional pituitary GHRH‐R levels found in younger rats but not necessarily with those of serum leptin, T4 and IGF‐I.