DOSE-RELATED PERSISTENT PROLIFEROGENIC ACTION OF CORTICOTROPHIN 1–24 IN NORMAL ADULT HUMAN ADRENOCORTICAL CELLS IN PRIMARY TISSUE CULTURE

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Abstract
Human adrenocortical cells in the absence of ACTH possessed very low basal [methyl-3H]-Tdr [thymidine] labeling indices/h and mitotic activities; both a 2 and a 7 day treatment with doses of ACTH 1-24 from 3 .times. 10-11-3 .times. mol/l upwards significantly and persistently increased the fractions of adrenocortical cells caught in the ''S'' and ''M'' phases of their growth-division cycle; at concentrations higher than 3 .times. 10-9-3 .times. 10-8 mol/l there was a significant fall in the mitotic coefficient. The effects of ACTH 1-24 on the apparent surface area of [methyl-3H]-Tdr-labeled nuclei. The Ag grain background of the autoradiographic specimens ranged from 0.9-2.3 grains/100 .mu.m2. The Ag grain density/100 .mu.m2 was significantly increased by ACTH 1-24 after both 2 and 7 days of treatment in a dose range of 3 .times. 10-11 and 3 .times. 10-8-3 .times. 10-7 mol/l; very low and high doses of the hormone left this parameter at control levels. ACTH, as soon as its level in plasma exceeds the physiological range, induces [3H]thymidine uptake and proliferation of normal adult human adrenocortical cells from zonae fasciculata and reticularis. The dose-related changes in the intensity of uptake of [3H]thymidine and of the mitogenic effect observed in vitro are probably due to rather complex hormonal mechanisms which need further study.

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