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Receptor binding of transforming growth factor-beta by human fetal adrenal cells
1Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 35233-7333, USA.
Abstract:
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)
Insights
Adrenocorticotropic hormone (ACTH) enhances transforming growth factor beta 1 (TGF-beta 1) binding to human fetal adrenal cells. This suggests ACTH may modulate TGF-beta 1
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor beta 1 (TGF-beta 1) inhibits human fetal adrenal (HFA) cell proliferation.
- Adrenocorticotropic hormone (ACTH) partially counteracts TGF-beta 1's antimitotic effect.
Purpose of the Study:
- To investigate if ACTH interferes with TGF-beta 1's action by altering its binding to adrenal cells.
- To elucidate the mechanism behind ACTH's modulation of TGF-beta 1's effects.
Main Methods:
- Incubation of HFA cells with 125I-labeled TGF-beta 1 at 4°C for varying durations.
- Assessment of TGF-beta 1 binding inhibition by unlabeled TGF-beta 1 and other cytokines.
- Treatment of HFA cells with ACTH, dibutyryl cAMP, or forskolin prior to TGF-beta 1 binding assays.
- Scatchard analysis to characterize TGF-beta 1 binding sites.
Main Results:
- TGF-beta 1 binding to HFA cells increased over time and was dose-dependently inhibited by unlabeled TGF-beta 1.
- ACTH pretreatment significantly increased specific 125I-labeled TGF-beta 1 binding.
- The ACTH-induced increase in TGF-beta 1 binding was maximal with 0.9 nM ACTH.
- Dibutyryl cAMP and forskolin mimicked the effect of ACTH on TGF-beta 1 binding.
- Scatchard analysis indicated ACTH treatment alters TGF-beta 1 binding site characteristics.
Conclusions:
- ACTH enhances TGF-beta 1 binding to HFA cells, suggesting a novel mechanism for its modulatory role.
- The findings imply that ACTH may influence TGF-beta 1 signaling pathways in the adrenal cortex.
- Further research is warranted to understand the physiological implications of altered TGF-beta 1 binding in the adrenal gland.
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