Effects of transforming growth factor-beta on human fetal adrenal steroid production.
Transforming growth factor-beta (TGF-beta) was found to inhibit basal and ACTH-stimulated steroid production by cultured human fetal adrenal cells. The inhibitory effects of TGF-beta were both time and dose-dependent. Inhibition of basal dehydroepiandrosterone sulfate (DS) production usually was noted only after 3 or more days of treatment with > or = 0.1 ng TGF-beta/ml. The inhibitory effects of 1 ng/ml TGF-beta on ACTH-stimulated DS production were more striking than those on cortisol production by both fetal zone and neocortical cells. TGF-beta also was found to interfere with DS and cortisol production by fetal zone cells in response to forskolin and dibutyryl cAMP. TGF-beta interfered with ACTH stimulation of cytochrome P450(17) alpha mRNA in fetal zone and neocortex cells. These results are suggestive that TGF-beta differentially inhibits DS and cortisol production by human fetal adrenal cells and that the site of TGF-beta action on steroidogenesis may be distal to the generation of cAMP. Such results, along with those of others, are suggestive that TGF-beta may play an autocrine/paracrine role in the human adrenal.
Stankovic
A K
AK
Department of Obstetrics and Gynecology, University of Alabama at Birmingham 35233-7333.
Dion
L D
LD
Parker
C R
CR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005576:Colforsin; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase; D000262:Adenylyl Cyclases; D006854:Hydrocortisone