ACTH and thyroid hormone regulation of 3 beta-hydroxysteroid dehydrogenase activity in human fetal adrenocortical cells.
The regulation of 3 beta-hydroxysteroid dehydrogenase, delta 4,5-isomerase (3 beta-HSD) and hydroxysteroid sulfotransferase (HST) activities by ACTH and thyroid hormones was investigated in cell cultures from the fetal zone or definitive zone of the human fetal adrenal cortex, using a serum-free, defined medium. ACTH alone maximally stimulated the 3 beta-HSD activity several-fold, whereas triiodothyronine (T3) alone had no effect on this enzyme activity in cell cultures from each zone. However, treatment of cultures with maximal concentrations of 10 nM ACTH plus 1 nM T3 significantly increased the 3 beta-HSD activity an additional 59-115% over that for ACTH alone, without alteration of the ACTH ED50 (0.3 nM). The T3 ED50 was 31 pM for this interaction with ACTH. Thyroxine at a reduced sensitivity had the same interaction with ACTH. T3 similarly increased the stimulation of 3 beta-HSD activity by the steroidogenic agents, cholera toxin and a cAMP analog. The HST activity was not affected by T3 alone but was stimulated by ACTH alone. This stimulation was an order of magnitude less than that for the 3 beta-HSD activity in the same cultures. ACTH plus T3 did not have the synergistic effect on HST activity as observed for the 3 beta-HSD activity. These studies show an interaction between ACTH and thyroid hormone for the stimulation of 3 beta-HSD activity in cell cultures of the human fetal adrenal cortex.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000196:embryology* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D013873:Thionucleotides; D014284:Triiodothyronine; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D013466:Sulfurtransferases; D015238:Sulfotransferases; C028152:alcohol sulfotransferase