Transgenic mice over-expressing galanin exhibit pituitary adenomas and increased secretion of galanin, prolactin and growth hormone

Abstract

Galanin is a biologically active 29 amino acid peptide, widely distributed in the central and peripheral nervous system, and most abundantly in the hypothalamus where it may serve in the regulation of anterior pituitary hormones. We herein report that mice carrying the rat preprogalanin cDNA specifically targeted to the somatomammotroph cell lineage, under the control of the rat GH promoter, over-express and over-secrete galanin. Galanin peptide is localised within the GH and prolactin secretory granules. GH and prolactin release is increased as well, predominantly in males, while older transgenic animals develop pituitary hyperplasia and adenoma. In both male and female transgenic mice there is a significant increase in serum galanin (P,0·00003 and P,0·001 respectively) and prolactin (P,0·002 and P,0·05 respectively) levels, while only in male transgenic mice is there a significant increase in the serum levels of GH. Furthermore, in male transgenic mice serum prolactin levels are significantly correlated with the serum galanin levels (P,0·03). We conclude that galanin plays a key role in the process of pituitary hyperplasia, acting as a growth factor to promote pituitary cell proliferation, and participates in pituitary adenoma formation not necessarily dependent on oestrogens. Targeted over-expression and over-secretion of galanin in the somatomammotroph cell lineage stimulates predominantly hyperprolactinaemia in an oestrogenindependent manner.

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…No difference in intact mechanical thresholds but higher after nerve injury, returned to intact values by day 7 (Bacon et al, 2007;Hulse et al, 2011) Reduction in acetone-induced pain-like behavior after PSNI (Hulse et al, 2012) Lower levels of cell death in vivo and in vitro (Elliott-Hunt et al, 2004) Decrease in opiate withdrawal behavior Galanin (inducible) (Pope et al, 2010)/tTA under control of 20 kb murine genomic galanin, 4.6 kb murine genomic galanin under control of tetO/CBA/BL6 F1 hybrid Increased mechanical thresholds after nerve injury reduced by galanin suppression (Pope et al, 2010) Growth hormone (Perumal and Vrontakis, 2003)/320 bp rat GH promoter driving full-length rat preprogalanin cDNA including poly A tail (4.5 kb transgene)/C57BL6/SJL F2 Â Swiss CD Increased serum levels of galanin, prolactin and GH (GH in males only) Pituitary hyperplasia and adenomas in older mice (Perumal and Vrontakis, 2003) Reduced CPZ-induced myelin breakdown (Zhang et al, 2012) Platelet-derived growth factor driving galanin (Holmberg et al, 2005a)/1.3 kb PDGF-b with galanin/GMAP gene construct, including intron 2 of the mouse galanin gene (genomic DNA and cDNA)/CBA/BL6 F1 hybrid Increase in learned helplessness in old mice (Pirondi et al, 2005b). Increase in learned helplessness (Kuteeva et al, 2005) Reduced neuronal loss postaxotomy, 35% reduction in plasma extravasation, increased response in phase 2 of formalin test (Holmberg et al, 2005a) Elevated thermal thresholds but no difference in mechanical thresholds or cold thermal in intact adults (Blakeman et al, 2001) Decreased response to evoked seizures (Kokaia et al, 2001) Delayed reduction in NA after intracerebroventricular injection of galanin to ventral hippocampus.…”

Molecular and Histological Studies of Pituitary Tumorigenesis Using Experimental Animal Models

“…However, estrogen-independent GH and PRL producing adenoma formation was suggested in the galanin Tg mouse [46]. Galanin is widely distributed in the central and peripheral nervous system, and most abundantly in the hypothalamus where it may serve in the regulation of anterior pituitary hormones [52].…”

Intrapituitary Regulatory System of Proliferation of Mammotrophs in the Pituitary Gland

“…Therefore, it is possible that galanin plays a paracrine role within the pituitary gland. The targeted over-expression of galanin in mouse pituitary cells increased the number of somatotrophs and mammotrophs, and serum PRL levels (Perumal and Vrontakis, 2003). These results suggest that galanin regulates PRL secretion and the proliferation of mammotrophs.…”