[The role of periodic changes in cyclase and protein kinase activity in the mechanism of the proliferative effect of ACTH].
A prolonged effect of ACTH on the state of adenylate and guanylate cyclase systems in the adrenal glands of experimental animals was investigated. It was found that in guinea pigs injected with ACTH (4 units daily for 1-50 days) the weight of adrenal glands and the DNA content in these organs increased 2.0-2.5-fold by the end of experiment; the increase in both values was stepwise. The corticosteroid level in the blood varied throughout the experiment: the changes in the DNA content in adrenals and in the corticosteroid content in the blood were oppositely directed. This was accompanied by cyclic changes in the basal and stimulated activities of adenylate and guanylate cyclases and proteinases in the adrenal glands occurring with a periodicity of 6-15 days. The activity peaks for cyclases and protein kinases preceded the rise in the DNA content in the adrenals. A clearcut correlation between the changes in the enzyme activity and the hormone dose was observed. The changes in the basal and stimulated activities of guanylate cyclase seem to be due to the control of cAMP level in the cell (stimulation of cGMP-dependent cAMP phosphodiesterase). Apparently, the periodic changes in the activity of cAMP-dependent protein kinases in the cytoplasmic and nuclear fractions and a relatively high activation of nuclear protein kinases (by 30-60%) in comparison of cytoplasmic ones (8-10%) are related to stimulation of DNA synthesis. It is concluded that the changes in the activity of cyclases and protein kinases play a role in the mechanism of proliferative effect of ACTH.
Smirnova
N B
NB
Gorshkova
T V
TV
Makarovskaia
E E
EE
Chekhranova
M K
MK
Afinogenova
S A
SA
D000263:Adenylate Kinase / Q000378:metabolism*; D000311:Adrenal Glands / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006168:Guinea Pigs; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D010770:Phosphotransferases; D011494:Protein Kinases; D000263:Adenylate Kinase
Rol' periodicheskikh izmeneniĭ aktivnosti tsiklaz i proteinkinaz v mekhanizme proliferativnogo deĭstviia AKTG.