Ghrelin restoration of function in vitro in somatotropes from male mice lacking the janus kinase (JAK)-binding site of the leptin receptor

Mohsin Syed, Michael Cozart, Anessa C. Haney, Noor Akhter, Angela K. Odle, Melody Allensworth-James, Christopher Crane, Farhan M. Syed, Gwen V. Childs

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Deletion of the signaling domain of leptin receptors selectively in somatotropes, with Cre-loxP technology, reduced the percentage of immunolabeled GH cells and serum GH. We hypothesized that the deficit occurred when leptin's postnatal surge failed to stimulate an expansion in the cell population. To learn more about the deficiency in GH cells, we tested their expression of GHRH receptors and GH mRNA and the restorative potential of secretagogue stimulation in vitro. In freshly plated dissociated pituitary cells from control male mice, GHRH alone (0.3 nM) increased the percentage of immunolabeled GH cells from 27 ± 0.05% (vehicle) to 42 ± 1.8% (P < .002) and the secretion of GH 1.8-3×. Deletion mutant pituitary cells showed a 40% reduction in percentages of immunolabeled GH cells (16.7±0.4%), which correlated with a 47% reduction in basal GH levels (50 ng/mL control; 26.7 ng/mL mutants P = .01). A 50% reduction in the percentage of mutant cells expressing GHRH receptors (to 12%) correlated with no orreduced responses to GHRH. Ghrelin alone (10 nM) stimulated more GH cells in mutants (from 16.7-23%). When added with 1-3 nMGHRH, ghrelin restored GH cell percentages and GH secretion to levels similar to those of stimulated controls. Counts of somatotropes labeled for GH mRNA confirmed normal percentages of somatotropes in the population. These discoveries suggest that leptin may optimize somatotrope function by facilitating expression of membrane GHRH receptors and the production or maintenance of GH stores.

Original languageEnglish (US)
Pages (from-to)1565-1576
Number of pages12
JournalEndocrinology
Volume154
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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    Syed, M., Cozart, M., Haney, A. C., Akhter, N., Odle, A. K., Allensworth-James, M., Crane, C., Syed, F. M., & Childs, G. V. (2013). Ghrelin restoration of function in vitro in somatotropes from male mice lacking the janus kinase (JAK)-binding site of the leptin receptor. Endocrinology, 154(4), 1565-1576. https://doi.org/10.1210/en.2012-2254