Effects of genotype on age-related alterations in the concentrations of stress hormones in plasma and hypothalamic monoamines in rats.
The adaptive response of the neuroendocrine system to stress is known to be impaired during ageing, and this impairment may be genetically determined. To elucidate further the effect of genotype, inbred male rats of the Wistar-Kyoto (WKY) strain, characterized by their hyper-reactivity to stressors and shorter life span, were compared with Brown-Norway (BN) rats. In young BN rats, resting prolactin concentrations were lower than in WKY animals and were reduced with age, while in WKY rats they remained unchanged with age. In young rats of both strains prolactin concentrations were highest after subjecting them to stressful stimuli for 15 min. After 2 h of restraint stress (during which the animals were confined to a narrow space that restricted movement) prolactin concentrations in young rats returned to pre-stress values, while remaining high in aged rats of both strains. Concentrations of corticotrophin (or adrenocorticotrophic hormone, ACTH) were lower in BN than in WKY rats and did not change with age in either strain. After 2 h of stress, ACTH concentrations were still slightly higher than normal in both young and aged BN rats, but not in WKY rats. Corticosterone concentrations were similar in young WKY and BN rats and were reduced in aged rats of both strains. After 2 h of stress, corticosterone concentrations were still high in aged, but not in young rats of both strains. However, this stress-induced increase was larger (3.7 times as much) in the BN strain than in the WKY strain (in which the increase was 1.7 times as much). The concentrations of hypothalamic monoamines were similar in young rats of both strains, although stress resulted in reduced noradrenaline concentrations, as previously documented, and in minor increases in 3,4-dihydroxyphenylacetic acid in both strains. During ageing, basal noradrenaline concentrations were reduced only in WKY rats, while the amount of 5-HT increased selectively in BN rats. Concentrations of 5-hydroxyindoleacetic acid were increased after stress in aged WKY rats only. The results demonstrate that resting plasma concentrations of the stress hormones ACTH and corticosterone and of prolactin are lower in BN than in WKY rats. In ageing, however, the stress-induced increases in the concentrations of these hormones are relatively higher in the BN strain, which is characterized by a longer life span.(ABSTRACT TRUNCATED AT 400 WORDS)
Gilad
G M
GM
Neuropsychiatry Branch, NIMH Neuroscience Research Center, St Elizabeth's Hospital, Washington, DC 20032.
Li
R
R
Wyatt
R J
RJ
Tizabi
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D005838:Genotype; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008136:Longevity; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000097:blood*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011914:Rats, Inbred BN; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism
D015306:Biogenic Monoamines; D010908:Pituitary Hormones, Anterior; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003345:Corticosterone; D009638:Norepinephrine