Neurotrophic ACTH analogue promotes plasticity of type I corticosteroid receptor in brain of senescent male rats.
Age-related changes were studied in the concentration of type-I and type-II corticosteroid receptors in the hippocampus of young adult (3 months) and aged (28.5 to 30.5 months) male rats. Using 3H-labelled ligands, in vitro binding of type-I and type-II corticosteroid receptors in the soluble cell fraction (cytosol) revealed an age-related decrease in concentration of both receptor types of 52% and 28%, respectively. Infusion of young and aged male rats for 2 weeks with the ACTH4-9 [adrenocorticotropin4-9] peptide analogue ORG 2766 (0.5 micrograms/0.5 microliter/hr) resulted in only a minor increase (+8%) in the number of type-I receptors in young rats. In the aged animals, however, the type-I receptor concentration was 68% higher than in the vehicle-treated aged animals. In contrast, no effect of the peptide treatment was noted on the concentration of type-II receptors in either young or aged rats. Furthermore, no effect was found for either age or treatment with peptide on the affinity of type-I and type-II receptors for their respective ligands. Binding of 3H-labelled ligands to brain sections of young and aged rats was performed using in vitro autoradiography. Quantitative image analysis of the film showed that in senescence there is a marked reduction in both type-I (62-75%) and type-II (29-56%) receptor concentrations in the hippocampal subregions (CA1, CA2, CA3 and dentate gyrus) as well as in the lateral septum. Treatment of aged rats with ORG 2766 selectively reversed the age-associated reduction in type-I receptors, while the peptide did not affect the type-II receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Reul
J M
JM
Rudolf Magnus Institute for Pharmacology, Faculty of Medicine, University of Utrecht, The Netherlands.
Tonnaer
J A
JA
De Kloet
E R
ER
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects*
D000927:Anticonvulsants; D010446:Peptide Fragments; D011965:Receptors, Glucocorticoid; C013765:Org 2766; D000324:Adrenocorticotropic Hormone