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Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors
Abstract:
Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.
Insights
Adrenocortical tumors show altered protein kinase activity, impacting response to ACTH. Defects in ACTH receptors or cAMP-dependent protein kinases can cause tumor dysfunction.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Adrenocortical tumors can exhibit resistance to adrenocorticotropic hormone (ACTH).
- Protein kinases play a crucial role in cellular signaling pathways, including steroidogenesis.
Purpose of the Study:
- To investigate protein kinase activity in human adrenocortical tumors.
- To compare kinase activity with normal adrenal tissue and correlate it with ACTH responsiveness.
Main Methods:
- Analysis of protein kinase activity in four human adrenocortical tumors and normal adrenal tissue.
- Assessment of ACTH receptor function and steroidogenesis response.
- DEAE-cellulose chromatography to resolve protein kinase isoenzymes.
Main Results:
- Two tumors with ACTH receptor anomalies had normal protein kinase activity.
- Two tumors with normal ACTH receptors showed altered protein kinase activity (either higher or lower basal and cAMP-stimulated levels).
- One tumor exhibited a loss of a specific cAMP-dependent protein kinase isoenzyme (II) and altered activation of another (I).
Conclusions:
- Lack of ACTH response in adrenocortical tumors can stem from ACTH receptor defects.
- Dysfunctional cAMP-dependent protein kinases are also implicated in adrenocortical tumor non-responsiveness to ACTH.