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Published on: October 2, 2018
Effects of transforming growth factor-beta 1 on human adrenocortical fasciculata-reticularis cell differentiated
M C Lebrethon1, C Jaillard, D Naville
1INSERM-INRA U-307, Hôpital Debrousse, Lyon, France.
Abstract:
Transforming growth factor-beta 1 (TGF beta 1) has been reported to have a strong inhibitory effect on the specific function of adrenal cells of several species. In the present study, we examined the effects of TGF beta 1 on cultured human fasciculata-reticularis cells. TGF beta 1 alone had no effect on ACTH receptor messenger ribonucleic acid (mRNA) levels and was unable to reduce the strong stimulatory effects of ACTH on its own receptor. However, TGF beta 1 enhanced angiotensin-II type 1 receptor mRNA and binding sites. Treatment with TGF beta 1 increased significantly the levels of 3 beta-hydroxysteroid dehydrogenase mRNA, reduced those of cytochrome P-450 17 alpha-hydroxylase mRNA, and had no effect on cholesterol side-chain cleavage cytochrome P-450 mRNA. Whatever the experimental condition, TGF beta 1 did not reduce basal or ACTH-stimulated cortisol production, but the production of dehydroepiandrosterone sulfate of TGF beta 1-treated cells was always decreased. The effects of TGF beta 1 on 3 beta-hydroxysteroid dehydrogenase mRNA and dehydroepiandrosterone sulfate were opposite the change observed at the time of adrenarche. As adrenal cells express TGF beta 1 mRNA, it is tempting to postulate that a local diminution of TGF beta 1 might be involved in adrenarche. Our findings also illustrate the specific species differences and, therefore, the caution to extrapolate to humans the results observed in other species.
Insights
Transforming growth factor-beta 1 (TGF beta 1) impacts human adrenal cells, altering specific steroidogenic enzyme mRNA levels and dehydroepiandrosterone sulfate production. A local decrease in TGF beta 1 may be involved in adrenarche.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor-beta 1 (TGF beta 1) is known to inhibit adrenal cell function in various species.
- Human adrenal fasciculata-reticularis cells' responses to TGF beta 1 require further investigation.
Purpose of the Study:
- To investigate the effects of TGF beta 1 on cultured human fasciculata-reticularis cells.
- To determine TGF beta 1's influence on specific gene expression and steroid hormone production.
Main Methods:
- Cultured human adrenal fasciculata-reticularis cells were treated with TGF beta 1.
- Messenger RNA (mRNA) levels for ACTH receptor, angiotensin-II type 1 receptor, 3 beta-hydroxysteroid dehydrogenase, cytochrome P-450 17 alpha-hydroxylase, and cholesterol side-chain cleavage cytochrome P-450 were analyzed.
- Steroid production (cortisol and dehydroepiandrosterone sulfate) was measured.
Main Results:
- TGF beta 1 did not affect ACTH receptor mRNA or ACTH-stimulated cortisol production.
- TGF beta 1 increased angiotensin-II type 1 receptor mRNA and enhanced 3 beta-hydroxysteroid dehydrogenase mRNA levels.
- TGF beta 1 decreased cytochrome P-450 17 alpha-hydroxylase mRNA and dehydroepiandrosterone sulfate production.
Conclusions:
- TGF beta 1 modulates specific gene expression and steroidogenesis in human adrenal cells.
- The observed effects of TGF beta 1 are distinct from those seen during adrenarche, suggesting a potential role for local TGF beta 1 reduction in this process.
- Species-specific differences in TGF beta 1 effects necessitate caution when extrapolating findings to humans.
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