Expression of VGF mRNA in developing neuroendocrine and endocrine tissues

Abstract

Analysis of knockout mice suggests that the neurotropininducible secreted polypeptide VGF (non-acronymic) plays an important role in the regulation of energy balance. VGF is synthesized by neurons in the central and peripheral nervous systems (CNS, PNS), as well as in the adult pituitary, adrenal medulla, endocrine cells of the stomach and pancreatic beta cells. Thus VGF, like cholecystokinin, leptin, ghrelin and other peptide hormones that have been shown to regulate feeding and energy expenditure, is synthesized in both the gut and the brain. Although detailed developmental studies of VGF localization in the CNS and PNS have been completed, little is known about the ontogeny of VGF expression in endocrine and neuroendocrine tissues. Here, we report that VGF mRNA is detectable as early as embryonic day 15·5 in the developing rat gastrointestinal and esophageal lumen, pancreas, adrenal, and pituitary, and we further demonstrate that VGF mRNA is synthesized in the gravid rat uterus, together supporting possible functional roles for this polypeptide outside the nervous system and in the enteric plexus.

In vitro and in vivo pharmacological role of TLQP‐21, a VGF‐derived peptide, in the regulation of rat gastric motor functions

“…As previously reported, the vgf gene is expressed in the GI tract and, during rat development, its expression was detected by in situ hybridization as early as embryonic day 15.5 in the developing rat GI tract and oesophageal lumen (Snyder et al. , 2003).…”

“…In the peripheral nervous system, the vgf gene is highly expressed in sympathetic, primary sensory neurons and in myenteric plexus ganglia, with evidence of expression in the glandular portion of the stomach, suggesting the presence of this gene throughout the gastrointestinal (GI) tract (Ferri et al, 1992;Liu et al, 1994;Salton et al, 2000;Snyder et al, 2003). Furthermore, pro-VGF fragments were described in human enterochromaffin-like cells, related hyperplastic and neoplastic cells (Rindi et al, 2007).…”

The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure

“…Increased circulating catecholamine levels in VGF-knockout mice could consequently be an indirect result of lower LDCV CgB content, and reported effects that this has of increasing circulating catecholamine levels and blood pressure in CgB-knockout mice (58), although it is important to note that the capacity to concentrate and secrete catecholamines, and adrenal epinephrine content, are all reduced in an independent line of CgB-knockout mice (59), so the observed increase in adrenal catecholamine content in VGF-knockout mice is unlikely to result from decreased CgB levels per se. Additional studies will be necessary to determine whether VGF modulation of the levels of CgB protein, catestatin, or perhaps a newly described CgB-derived peptide, hCHGB [60][61][62][63][64][65][66][67] (58), that inhibits catecholamine release in response to acetylcholine, are involved in BP regulation by VGF.…”

VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

“…In vivo, VGF mRNA is expressed in discrete, neurotrophinresponsive neurons early in embryogenesis, later in spinal cord, cranial nuclei, basal forebrain, adrenal, pituitary, stomach and pancreas (Snyder et al, 1998a(Snyder et al, , 2003. Expression is initially limited to limbic cortical areas, and later extends to sensory and motor areas (Eagleson et al, 2001).…”