The inducible gene vgf and its peptide products are relevant to the neuroendocrine regulation of homeostasis and reproduction in rodents. We show here that in the anterior pituitary of female sheep the somatotrope, gonadotrope, and lactotrope/thyrotrope cell populations each expressed vgf mRNA, but displayed a distinct profile of VGF immunoreactive peptides. ProVGF C-terminus and VGF_443–588 immunoreactivities were found in lactotropes and thyrotropes, often in a subcellular location restricted to the Golgi area and suggestive of rapid peptide (or proVGF) release upon biosynthesis, while high molecular weight bands consistent with proVGF were shown in pituitary extracts. Distinct seasonal changes were revealed, proVGF C-terminus immunoreactive cells being largely identified as lactotropes during the summer (83.7 ± 2.1% (mean ±s.e.m.) versus 27.0 ± 1.9% during the winter), as opposed to thyrotropes during the winter (73.0 ± 1.9% versus 16.3 ± 2.1% during the summer). Conversely, antisera to peptides adjacent to the ‘Arg-Pro-Arg’ cleavage site, and to the VGF_553–555 N-terminus of the proVGF-derived peptide V, selectively labeled gonadotropes, indicating processing to small peptides not retaining the proVGF C-terminus in such cells. Finally, a peptide related to the VGF_4–240 region was immunostained in somatotropes, shown in a Western blot as a band of relative molecular mass of approximately 16 000. In conclusion, a complex, endocrine cell-type-specific processing of proVGF was revealed. Further to the known inducibility of vgf mRNA upon a range of stimuli, discreet, selective modulations of VGF-peptide profile/s are suggested, possibly involved in specific neuro/endocrine or modulatory mechanisms.

Although vgf gene knockout mice are hypermetabolic, administration of the VGF peptide TLQP-21 itself increased energy consumption. Agonist–antagonist roles are thus suggested for different VGF peptides, and the definition of their tissue heterogeneity is mandatory. We studied the rat stomach using antisera to C- or N-terminal sequences of known or predicted VGF peptides in immunohistochemistry and ELISA. TLQP (rat VGF_{556 – 565}) peptide/s were most abundant (162±11 pmol/g, mean±s.e.m.) and were brightly immunostained in enterochromaffin-like (ECL) cells and somatostatin cells. A peptide co-eluting with TLQP-21 was revealed in HPLC of gastric and hypothalamic extracts, while the extended TLQP-62 form was restricted to the hypothalamus. Novel PGH (rat VGF_{422 – 430}) peptide/s were revealed in ghrelin cells, mostly corresponding to low MW forms (0.8–1.5 kDa), while VGF C-terminus peptides were confined to neurons. VGF mRNA was present in the above gastric endocrine cell types, and was prominent in chief cells, in parallel with low-intensity staining for further cleaved products from the C-terminal region of VGF (HVLL peptides: VGF_{605 – 614}). In swine stomach, a comparable profile of VGF peptides was revealed by immunohistochemistry. When fed and fasted rats were studied, a clear-cut, selective decrease on fasting was observed for TLQP peptides only (162±11 vs 74±5.3 pmol/g, fed versus fasted rats, mean±s.e.m., P<0.00001). In conclusion, specific VGF peptides appear to be widely represented in different gastric endocrine and other mucosal cell populations. The selective modulation of TLQP peptides suggests their involvement in peripheral neuro-endocrine mechanisms related to feeding responses and/or ECL cell regulation.