Increased affinity of type II corticosteroid binding in aged rat hippocampus.
Hippocampal tissue from young-mature (3-4 months old) and aged (24-26 months old) Fischer-344 rats was assessed for type I and type II corticosteroid binding in cytosol, using [3H]dexamethasone and selective inhibition of type II sites with nonradioactive RU-28362. Twenty-four hours after adrenalectomy, the Bmax and Kd of the receptor subtypes were measured by Scatchard analysis for individual animals. The binding capacity of each receptor type was significantly reduced in aged rats, as others have reported. In addition, however, the dissociation constant (Kd), was significantly reduced for type II receptor (young Kd = 2.14 nM vs aged Kd = 0.89 nM, P less than 0.005), indicating greater affinity of type II sites with aging. Affinity of type I sites was unchanged. The observation of increased type II affinity could help to explain the apparent paradox of why corticosteroid-dependent degenerative changes in hippocampal cells seem to accelerate in the later stages of aging, even though brain corticosteroid receptor capacity has been reported to decline or remain unchanged with aging.
Landfield
P W
PW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103.
Eldridge
J C
JC
D000315:Adrenalectomy; D000375:Aging / Q000378:metabolism*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*
D000732:Androstanols; D011965:Receptors, Glucocorticoid; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone