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Characterization of the inhibitory effect of glucocorticoids on the DNA replication of adult rat hepatocytes growing at various cell densities
Author(s) -
Vintermyr Olav Karsten,
Døskeland Stein Ove
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041380106
Subject(s) - dexamethasone , glucocorticoid , dna synthesis , medicine , steroid , endocrinology , antiglucocorticoid , hepatocyte , steroid hormone , glucocorticoid receptor , biology , cell culture , dna , basal (medicine) , testosterone (patch) , chemistry , in vitro , hormone , biochemistry , genetics , insulin
Dexamethasone inhibited the basal and EGF‐stimulated DNA synthesis of adult rat hepatocytes in primary culture. The inhibition was glucocorticoid‐specific: It was shown by dexamethasone and hydrocortisone, but not by progesterone, testosterone, or estradiol; and was counteracted by the glucocorticoid antagonist RU‐38486 in a concentration‐dependent manner. Dexamethasone acted by decreasing the rate of entry into S‐phase (k G1/S ), while cell cycle parameters were unaffected. The steroid was able to decrease the k G1/S severalfold even when added more than 20 hr after EGF, half‐maximal effect occurring 11 hr after the addition of dexamethasone. Densily populated areas were much more sensitive to the inhibition by dexamethasone than sparsely populated areas within the same culture dish: A moderate (10 nM) concentration of dexamethasone nearly abolished the DNA synthesis in densily populated areas of hepatocyte cultures with only marginal effect on sparsely populated cells.