Study summary · research use only
Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, the authors examined neuronal M3 muscarinic acetylcholine receptors in somatotroph proliferation and growth. Mutant mice selectively lacking the M3 receptor in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype with pronounced anterior pituitary hypoplasia and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. The abstract reports that treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit by restoring normal pituitary size and normal serum GH and IGF-1 levels. Together with M3 receptor/GHRH colocalization and hypothalamic hormone measurements, the authors describe a model in which central M3 receptors are required for proper function of hypothalamic GHRH neurons, indicating a role for central M3 receptors in regulating longitudinal growth by promoting somatotroph proliferation.
Abstract
The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.
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