Plasticity of pituitary hormone secretion, expression and cell numbers within the anterior pituitary glands of human growth hormone-releasing hormone transgenic mice: Focus on galanin, growth hormone, and prolactin.

摘要

Galanin is localized within the anterior pituitary gland of male and female rats, where it is dramatically upregulated by estrogen. Chronic exposure to estrogen eventually results in pituitary tumors. The human growth hormone-releasing hormone (hGHRH) transgenic mouse is chronically exposed to elevated levels of GHRH and develops a pituitary adenoma before one year of age. We utilized the male hGHRH transgenic mouse as an estrogen-independent model of pituitary formation in which to further study galanin, growth hormone (GH), prolactin, and the development of pituitary tumors. For comparisons, non-transgenic siblings were used as controls.;Utilizing the cell immunoblot assay, we determined that individual pituitary cells from transgenic mice secrete significantly greater amounts of galanin and GH. Galanin peptide concentrations were determined to be significantly higher within the anterior pituitary and hypothalamus, but not the neurointermediate lobe, of the hGHRH transgenic mouse. Galanin messenger ribonucleic acid (mRNA) levels were significantly increased within the pituitary of transgenic mice. Immunocytochemical techniques revealed that the percentage and number of galanin-containing pituitary cells were significantly increased within the hGHRH transgenic mice.;The majority of cells containing galanin also contained GH. Galanin peptide was also colocalized, to a smaller extent, within cells containing prolactin and thyroid-stimulating hormone in both transgenic and control mice. Further analysis of the colocalization of galanin with GH revealed that in transgenic and control animals, somatotrophs containing galanin secrete more GH than those devoid of galanin peptide. This result suggests that galanin of pituitary origin may have a role in the regulation of GH secretion.;The tumor that develops in hGHRH transgenic mice begins as a hyperplasia of all of the specific pituitary hormone cell types and progresses to a frank adenoma that consists of one primary cell type. The significant increase of pituitary galanin mRNA, peptide concentrations, and secretion are correlated with the hyperplasia of the pituitaries in hGHRH transgenic mice. Due to this and its regulatory influences on the secretion of GH, we hypothesize that galanin may have a role in the development and/or maintenance of pituitary tumors in hGHRH transgenic mice.