Effects of 5-bromodeoxyuridine on the ACTH-dependent mitochondrial biogenesis in cortical cells of fetal rat adrenals in tissue culture.

Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected.