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.

The intracellular domains of the membrane-anchoring regions of some precursors of epidermal growth factor (EGF) family members have intrinsic biologic activities. We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as part of the proEGF transmembrane-anchored region (proEGFctF) in the regulation of motility and elastinolytic invasion in human thyroid cancer cells. We found proEGFctF to act as a negative regulator of motility and elastin matrix penetration and the presence of proEGFcyt or proEGF22.23 resulted in a similar reduction in motility and elastinolytic migration. This activity was counteracted by EGF-induced activation of EGF receptor signaling. Decreased elastinolytic migratory activity in the presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with decreased secretion of elastinolytic procathepsin L. The presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with the specific transcriptional up-regulation of t-SNARE member SNAP25. Treatment with siRNA-SNAP25 resulted in motility and elastin migration being restored to normal levels. Epidermal growth factor treatment down-regulated SNAP25 protein by activating EGF receptor-mediated proteasomal degradation of SNAP25. These data provide first evidence for an important function of the cytoplasmic domain of the human proEGF transmembrane region as a novel suppressor of motility and cathepsin L-mediated elastinolytic invasion in human thyroid carcinoma cells and suggest important clinical implications for EGF-expressing tumors.

Galanin is a highly conserved neuropeptide with a wide range of biological effects. Recently, through transcriptome analysis, galanin was identified in undifferentiated mouse embryonic stem cells as one of the most abundant transcripts. We have examined the developmental expression of galanin-like immunoreactivity in mice from embryonic day 10 (E10) to embryonic day 15 (E15). At E10, galanin was readily detected in the undifferentiated head and trunk mesenchyme of both mesodermal and neural crest origin. There was also strong immunoreactivity in the mesenchymal spiral ridges of the outflow tract of the heart and the endocardial cushions. The highest level of galanin detected was at E13 in the craniofacial mesenchyme and proliferating chondrocytes in bones of both neural crest and mesoderm origin. Dorsal root ganglia and trigeminal ganglia contained galanin immunoreactive cells as well. These data indicate the presence of galanin peptide during periods of morphogenesis and thus a developmental role for the peptide in mesenchymal and neural crest origin tissues in the mouse embryo. Whether galanin has a growth and/or differentiating role, still remains to be demonstrated. Anat Rec, 292:481-487, 2009Rec, 292:481-487, . 2009 Wiley-Liss, Inc.

There have been few Golgi studies dealing with the cytoarchitecture of the supraoptic nucleus (SON). This is due in part to resistance of supraoptic neurons to impregnation by Golgi methods. In this study, the structure of the SON was examined in normal S/D rats by using both Nissl and Golgi-silver methods. The purpose was to correlate shape, size and location of neurons within the SON as revealed by these two techniques. On the basis of size, neurons of the SON can be divided into 3 populations: greater than 200 micron2, (9%); 100-200 micron2, (64%); and less than 100 micron2, (27%). The larger neurons are located predominantly at mid-nuclear levels; the smaller at rostral and caudal levels of the nucleus. The perikarya of most SON neurons (64%) are only slightly elliptical in cross-section (L/W less than or equal to 2). The large neurons, however, tend to be more spherical whereas the smaller neurons are more elongated (L/W greater than or equal to 3). In Golgi preparations, a variety of randomly distributed bipolar and multipolar neurons were identified. One form of bipolar neuron had a large spherical or oval cell body that was intimately associated with blood vessels. Its thick, varicose dendrites usually lacked spines and were not extensively branched. A second form of bipolar neuron was distinguished by its smaller more fusiform cell body and lengthy dendrites which were often spinous and more extensively branched. Axons, when present emerged from the cell body or a proximal dendrite and were uniformly thin except for fusiform swellings along their length. Among multipolar neurons, the following variants were distinguished: spherical and polygonal neurons of various sizes with 3-5 dendrites and small triangular neurons with dendrites arising from each of the poles. The results of this study demonstrate the heterogeneity of the rat SON and of its neuronal components, some of which appear suited to function in a nonendocrine capacity, possibly as interneurons.