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ROLE OF ADENYLATE-CYCLIC AMP-PROTEIN KINASE A IN THE INCREASE OF CORTICOSTERONE SECRETION IN RAT ZONA FASCICULATA-RETICULARIS CELLS BY AGING.
Lo, Ming-Jae1, Kau, Mei-Mei2, Wang, Paulus3, 1 2 3
ABSTRACT- The effects and action mechanisms of aging on corticosterone secretion in ovariectomized (Ovx) rat zona fasciculata-reticularis (ZFR) cells were studied. Young (3-month) and old (24-month) female rats were Ovx for 4 days before decapitation. ZFR cells were isolated and incubated with different hormones or agents for 30 or 60 min. Aging increased basal secretion of corticosterone both in vivo and in vitro. The adrenocorticotropin (ACTH)-, forskolin (FSK, an activator of adenylyl cyclase)-, 3-isobutyl-l-methylxanthine (IBMX, an inhibitor of phosphodiesterase)-, 8-bromo-adenosine 3′:5′-cyclic monophosphate (8-Br-cAMP, an analog of membrane-permeable cAMP)-, H89 (an inhibitor of protein kinase A)-, and prolactin (PRL)-induced release of corticosterone by ZFR cells for 30 or 60 min was greater in old than in young Ovx rats. FSK-, or IBMX-induced production of cAMP for either 30 or 60 min was greater in old than in young Ovx animals, which correlated with the increase of corticosterone production. However, there was no difference in ACTH-stimulated production of cAMP for 60 min between old and young Ovx rats. PRL-stimulated cAMP production for 60 min was lower in old than in young Ovx rats. These results suggest that age-related increase of corticosterone production in Ovx rats is associated with an increased activity of adenylate-cAMP/protein kinase A pathway and a stimulatory effect of PRL on ZFR cells.
KEY WORDS: aging, corticosterone, cAMP, PKA