Differential effects of aging on adrenocorticotropin receptors, adenosine 3'5'-monophosphate response, and corticosterone secretion in adrenocortical cells from Sprague-Dawley rats.
This study examined the effect of aging on adrenal cell function in Sprague-Dawley rats, as judged by the binding of iodinated Phe2, Nle4-ACTH-(1-38) to the adrenal cells, and the ability of the cells to respond to ACTH stimulation by the production of cAMP and corticosterone in vitro. Collagenase-dispersed adrenal cells obtained from 2-, 12-, and 18-month-old-rats were used. The maximum corticosterone concentration after incubation with ACTH was significantly lower (P less than 0.001) in the 12-month-old (40 +/- 7 ng/micrograms DNA) and 18-month-old rats (28 +/- 3 ng/micrograms DNA) compared to that in 2-month-old controls (102 +/- 9 ng/micrograms DNA). The ED50 values of ACTH-induced corticosterone production measured in the cell suspension were similar in 2- and 12-month-old groups (30 pg/ml), and the diminished production of corticosterone in the 12-and 18-month-old rats persisted after incubation with N6,O2-dibutyryl cAMP. Neither the number nor the binding affinity of adrenal receptors for [125I]I-Tyr23,Phe2,Nle4-ACTH-(1-38) changed from 2-12 months of age. Furthermore, increases in concentrations of intra- and extracellular cAMP after ACTH stimulation were not significantly different in the 2-, 12-, and 18-month-old groups. Similarly, adrenal hydrolysis of cAMP by low and high Km phosphodiesterases did not change significantly with advancing age. These results provide strong evidence that there is a diminished capacity for corticosterone production with aging in the rat, and that the site of the defect lies distal to binding of trophic hormone to its receptor and to the production of its secondary messenger. Finally, an age-related decline in adrenal steroidogenic capacity could be viewed as a counterregulatory mechanism invoked in old rats to compensate, at least partially, for elevated plasma ACTH and corticosterone concentrations.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000378:metabolism; D000375:Aging; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology*; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone / Q000502:physiology*
D010446:Peptide Fragments; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone; D003994:Bucladesine; C030701:ACTH (1-38), Phe(2)-Nle(4)-; C030702:ACTH (1-38), Phe(2)-Nle(4)-iodo-Tyr(23)-; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D003345:Corticosterone