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[The role of Ca2+ in the pathogenesis of human pituitary GH-secreting adenomas]
Abstract:
Effects of Ca2+ channel blockers (nicardipin and nifedipin) and Ca2+ ionophore A23187 on the basal secretion and on the secretion stimulated by GRH or inhibited by SMS, a SRIF analogne of GH were investigated in monolayer cell cultures of 23 cases of human pituitary GH-secreting adenomas. The roles of GRH and SMS in 45Ca influx were investigated also. The GH secretion of most GH adenomas was depended on Ca2+, but the abnormality in different link of GH secretion mediated by Ca2+ was observed. The defects of receptor and post-receptor including Ca2+ channel and Ca(2+)-GH secretion couple regulated by GRH and SRIF were found in 66.7% and 55.6% of GH adenomas respectively. These abnormalities may contribute to GH hypersecretion in GH adenomas.
Insights
Calcium channel blockers and ionophores reveal defects in growth hormone (GH) secretion pathways in pituitary adenomas. Abnormalities in calcium signaling contribute to excessive GH release in most GH-secreting adenomas.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Medicine
Background:
- Pituitary adenomas secreting growth hormone (GH) cause significant health issues.
- Understanding the mechanisms of GH hypersecretion is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of calcium (Ca2+) in the regulation of GH secretion in human pituitary GH-secreting adenomas.
- To identify defects in calcium signaling pathways that may lead to abnormal GH release.
Main Methods:
- Monolayer cell cultures from 23 human pituitary GH-secreting adenomas were used.
- Effects of Ca2+ channel blockers (nicardipine, nifedipine) and Ca2+ ionophore A23187 on basal and stimulated GH secretion were assessed.
- The influence of growth hormone-releasing hormone (GRH) and somatostatin analog (SMS) on 45Ca influx was examined.
Main Results:
- GH secretion in most adenomas was dependent on Ca2+.
- Abnormalities were observed in various links of Ca2+-mediated GH secretion.
- Defects in receptors and post-receptor signaling, including Ca2+ channels and Ca2+-GH secretion coupling, were found in a significant percentage of adenomas (66.7% and 55.6% respectively).
Conclusions:
- Calcium signaling plays a critical role in regulating GH secretion in pituitary adenomas.
- Defects in calcium-dependent pathways are common in GH-secreting adenomas and likely contribute to GH hypersecretion.