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Transforming growth factor beta treatment decreases ACTH receptors on ovine adrenocortical cells
W E Rainey1, I Viard, J M Saez
1Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235.
Abstract:
Transforming growth factor beta (TGF beta) is a potent inhibitor of adrenocortical cell differentiated functions, whereas corticotropin (ACTH) is the main physiological hormone which acts positively on these functions. We have studied the effects of both TGF beta and ACTH on ovine adrenocortical cell ACTH receptors. Ovine adrenocortical cells contained specific high affinity (Kd = 2.7 +/- 1.6 x 10(-10) M) and low capacity (1190 +/- 120 sites/cell) ACTH receptors. Pretreatment of cells with TGF beta resulted in a time- and dose-dependent (ED50 = 50 pg/ml) decrease of 125I-ACTH1-39 binding. The observed decrease in ACTH binding was due to a 2-3-fold decrease in the number of binding sites without modification of the binding affinity. On the contrary, pretreatment of cells with ACTH caused a 4-4.5-fold increase in the number of ACTH binding sites without an effect on the Kd. When cells were pretreated with both ACTH and TGF beta, TGF beta blocked completely the positive trophic effect of ACTH on its own receptors. The variations in ACTH receptor number were associated with parallel changes on acute ACTH-induced cyclic AMP production. Thus, the effects of TGF beta on ACTH receptor content are likely another important negative action of this peptide on adrenocortical cell differentiation. Moreover, these results suggest that regulation of ACTH receptor number may be one mechanism by which hormones and growth factors control adrenocortical differentiation.
Insights
Transforming growth factor beta (TGF beta) inhibits adrenocortical cell functions by decreasing ACTH receptors. It also blocks the positive effect of ACTH on its own receptors, impacting cell differentiation.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Signaling
Background:
- Adrenocortical cell function is regulated by hormones like corticotropin (ACTH) and growth factors.
- Transforming growth factor beta (TGF beta) is known to inhibit differentiated functions in adrenocortical cells.
Purpose of the Study:
- To investigate the effects of TGF beta and ACTH on ACTH receptors in ovine adrenocortical cells.
- To understand the regulatory mechanisms of ACTH receptor expression and its impact on adrenocortical cell differentiation.
Main Methods:
- Ovine adrenocortical cells were used to study ACTH receptors.
- Cells were pretreated with TGF beta and/or ACTH.
- Binding assays with 125I-ACTH1-39 were performed to quantify receptor number and affinity.
- ACTH-induced cyclic AMP production was measured.
Main Results:
- Ovine adrenocortical cells possess specific, high-affinity ACTH receptors.
- TGF beta significantly decreased ACTH receptor number in a time- and dose-dependent manner, without altering binding affinity.
- ACTH increased the number of its own receptors, but TGF beta blocked this effect.
- Changes in ACTH receptor number correlated with changes in ACTH-stimulated cyclic AMP production.
Conclusions:
- TGF beta negatively impacts adrenocortical cell differentiation by reducing ACTH receptor content.
- Regulation of ACTH receptor number is a key mechanism through which hormones and growth factors modulate adrenocortical cell differentiation.