Galanin gene expression is increased in the anterior pituitary gland of the human growth hormone-releasing hormone transgenic mouse.
The peptide galanin is synthesized within and secreted from specific cells of the anterior pituitary gland. Previous studies showed that GH-releasing hormone (GHRH) stimulates galanin release from pituitary cells in vitro. In the present study we used human (h) GHRH transgenic mice to examine the effects of high circulating levels of GHRH on pituitary galanin gene expression in vivo. Moreover, the hGHRH transgenic mice develop pituitary tumors and, thus, may be used as a model of estrogen-independent pituitary adenoma formation. We examined male hGHRH transgenic mice and nontransgenic siblings at 2, 4, 6, 8, and 10 months of age. Transgenic mice were identified using the polymerase chain reaction. Body weights and plasma mGH levels were higher in transgenic mice at all ages. Total protein contents in the anterior pituitary glands of transgenic mice were significantly greater at each age. Galanin peptide contents in the anterior pituitary gland of hGHRH mice were normalized for differences in total protein content and were significantly elevated at all ages examined. At 10 months of age, anterior pituitary galanin peptide concentrations were increased 7-fold. Hypothalamic concentrations of galanin peptide were also increased in hGHRH transgenic mice, but were not greater than those in nontransgenic siblings until 4 months of age. In contrast, no significant differences in galanin peptide concentrations of the neurointermediate lobes were evident. Galanin mRNA concentrations in the anterior pituitary of 6-month-old transgenic mice were increased 4-fold. In conclusion, 1) galanin peptide concentrations in the anterior pituitary gland and hypothalamus are increased in hGHRH transgenic mice compared to those in nontransgenic siblings, whereas galanin peptide concentrations in the neurointermediate lobe are not different; 2) pituitary galanin mRNA concentrations are increased 4-fold in 6-month-old transgenic mice; and 3) the development of pituitary hyperplasia is correlated to the increase in galanin mRNA and peptide concentrations.
Moore
J P
JP
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536.
Morrison
D G
DG
Hyde
J F
JF
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D005260:Female; D019004:Galanin; D015870:Gene Expression; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism
D010455:Peptides; D011506:Proteins; D019004:Galanin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone