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Functional defects in mice somatotropes caused by ablation of leptin receptors is reversed, in vitro, by stimulation with Ghrelin
Author(s) -
Syed Mohsin M,
Cozart Michael A,
Crane Christopher,
Haney Anessa C,
Akhter Noor,
Odle Angela K,
Syed Farhan M,
Allensworth Melody,
Childs Gwen V
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.909.4
Subject(s) - medicine , ghrelin , endocrinology , somatotropic cell , stimulation , receptor , leptin , biology , growth hormone–releasing hormone , hormone , in vitro , chemistry , pituitary gland , growth hormone , biochemistry , obesity
Deletion mutant mice without leptin receptors on somatotropes (GH cells) have fewer immunolabeled GH cells. This study determined if stimulation will restore GH cells, in vitro. Freshly dissociated pituitaries from male mice were stimulated for 3 h with 0.1–30 nM growth hormone releasing hormone (GHRH) either alone or with ghrelin (10nM). Media were immunoassayed for GH (Millipore, Inc). GHRH (0.3 nM) increased % of immunolabeled GH cells from 33±0.05% (vehicle) to 43±1.8% (p<0.002) in control cells, which secreted 1.79–4X more GH in response to 0.3—10 nM GHRH. Deletion mutant pituitaries contained 16.7±0.4% immunolabeled GH cells, which correlated well with their lower basal GH secretion (8 ng/ml in controls vs 4.9 ng/ml in the mutants p<0.03). GHRH (1–10 nM) restored the immunolabeled GH cells to 30–31% of pituitary cells (30% below levels in stimulated controls) Ghrelin alone stimulated more GH cells in mutants (23%) and enhanced the actions of 0.1—10 nM GHRH resulting in % of GH cells similar to those in the stimulated controls. Ghrelin enhanced secretory actions of 0.3–10 nM of GHRH, resulting in GH levels from mutant cultures equal to that seen in control cultures. These findings indicated that without leptin receptors, somatotropes are quiescent and less responsive to GHRH, suggesting leptin's importance in somatotrope function. This functional deficiency can be reversed in vitro by stimulation with ghrelin.