Receptor binding of transforming growth factor-beta by human fetal adrenal cells.
We have shown previously that transforming growth factor beta 1 (TGF-beta 1) is antimitotic for human fetal adrenal (HFA) cells in vitro and that this effect can be partially blocked by adrenocorticotropic hormone (ACTH). In the present study, we sought to determine whether ACTH might interfere with TGF-beta 1 action by means of reducing TGF-beta 1 binding to adrenal cells. We incubated adrenal cells with 50 pM 125I-labeled TGF-beta 1 for 15 min to 3 h at 4 degree C and found that the binding of 125I-labeled TGF-beta 1 increased with time and could be inhibited in a dose-dependent manner by non-labeled TGF-beta 1 (0.05-10 nM), but not with other relevant cytokines: IL6, TNF alpha,IGF-I, IGF-II, TGF-alpha, and EGF. Pretreatment of HFA cells with ACTH (0.009-900 nM) for 4-24 h significantly increased specific 125I-labeled TGF-beta 1 binding compared to that in untreated cells; maximal increases in binding were achieved with 0.9 nM ACTH. This effect of ACTH could be mimicked by treatment of adrenal cells with dibutyryl cAMP (1 mM) or forskolin (10 microM). Scatchard analysis of data from ACTH-treated cells suggest the presence of two populations of TGF-beta 1 binding sites with different affinity and capacity of binding for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
Stanković
A K
AK
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 35233-7333, USA.
Parker
C R
CR
D000302:Adrenal Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D001665:Binding Sites; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000196:embryology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003366:Cosyntropin; D005576:Colforsin; D003994:Bucladesine