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Somatostatin actions on a protein kinase C-dependent growth hormone secretagogue cascade
1Department of Biological Sciences, CW 405 Biological Sciences Building, Faculty of Science, University of Alberta, Edmonton, T6G 2E9, Alberta, Canada.
Abstract:
In mammals, the ability of somatostatin (SS) to block growth hormone (GH) secretion is due, in part, to the inhibition of two key intracellular mediators, cAMP and Ca2+. We examined whether or not inhibition of Ca2+ signaling was mediating SS-induced inhibition basal, as well as gonadotropin-releasing hormone (GnRH; a protein kinase C (PKC)-dependent growth hormone secretagogue)-stimulated growth hormone (GH) release. Although SS reduced basal GH release from populations of pituitary cells, parallel reductions in [Ca2+]i were not observed within single, identified somatotropes. Similarly, application of GnRH and the PKC activator DiC8 elicited increases in [Ca2+]i and GH release, but abolition of the Ca2+ responses did not accompany SS inhibition of the GH responses. Surprisingly, while DiC8 potentiated SS inhibition of GH release, SS paradoxically increased DiC8-stimulated increases in [Ca2+]i. These data establish that abolition of Ca2+ signals is not a primary mechanism through which SS lowers basal, or inhibits GnRH-stimulated hormone release.
Insights
Somatostatin (SS) inhibits growth hormone (GH) release but not by blocking calcium (Ca2+) signals. This study found SS does not reduce Ca2+ levels in single pituitary cells, even when inhibiting GH release.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Signaling
Background:
- Somatostatin (SS) is known to inhibit growth hormone (GH) secretion in mammals.
- This inhibition is partly attributed to the modulation of intracellular mediators like cyclic adenosine monophosphate (cAMP) and calcium (Ca2+).
- The precise role of Ca2+ signaling in SS-mediated inhibition of basal and stimulated GH release requires further elucidation.
Purpose of the Study:
- To investigate whether the inhibition of Ca2+ signaling mediates the effects of somatostatin (SS) on basal and gonadotropin-releasing hormone (GnRH)-stimulated growth hormone (GH) release.
- To determine the relationship between Ca2+ signaling and SS action in pituitary somatotropes.
Main Methods:
- Primary pituitary cell cultures were used to assess GH release.
- Intracellular calcium ([Ca2+]i) levels were measured in single, identified somatotropes using calcium imaging.
- GnRH and DiC8 (a protein kinase C activator) were applied to stimulate GH release and modulate Ca2+ signaling.
Main Results:
- SS reduced basal GH release from pituitary cell populations, but parallel reductions in [Ca2+]i were not observed in individual somatotropes.
- GnRH and DiC8 increased both [Ca2+]i and GH release; however, SS inhibited GH release without abolishing these Ca2+ responses.
- Paradoxically, SS potentiated SS inhibition of GH release while increasing DiC8-stimulated [Ca2+]i.
Conclusions:
- The abolition of Ca2+ signals is not the primary mechanism by which SS lowers basal GH release.
- SS does not primarily inhibit GnRH-stimulated GH release by blocking Ca2+ signaling pathways.
- These findings suggest alternative or parallel mechanisms are involved in somatostatin's regulation of growth hormone secretion.