Transgenic mice overexpressing the growth-hormone-releasing hormone gene have high concentrations of tachykinins in the anterior pituitary gland

According to recent reports, substance P (SP) is localized in the anterior pituitary gland within subsets of thyrotropes and somatotropes, although ea rlier electron-microscopic studies described the presence of this tachykini n in mammotropes and gonadotropes. Transgenic mice overexpressing the growt h-hormone-releasing hormone (GHRH) gene have markedly enlarged pituitary gl ands, due to hyperstimulation of the somatotropes. Therefore, we speculated that if somatotropes are able to synthesize tachykinins, these peptides sh ould be greatly increased in the anterior pituitary of transgenic GHRH mice . We found that, in accordance with our working hypothesis, both SP and neu rokinin A (NKA) were markedly increased in the anterior pituitary gland of male a nd female transgenic mice, compared with their respective normal con trols. In male transgenic mice, NKA was 13.6- and SP 20.2-fold higher than in the anterior pituitary from normal mice. In female transgenic mice, NKA was 40- and SP 100-fold higher than in the anterior pituitary from normal f emale mice. In male transgenic mice, NKA and neuropeptide K (NPK) contents in the anterior pituitary showed no significant changes between 26 and 50 d ays of age but significantly increased between 50 days and 5 months of age. The concentration of NKA in the anterior pituitary did not show significan t differences between 26 days and 5 months of age, but NPK concentrations i n the anterior pituitary significantly decreased with age. In female transg enic mice, NKA content and concentration in the anterior pituitary increase d after 35 days of age, but NPK concentrations significantly decreased afte r 26 days of age. Triiodothyronine markedly decreased anterior pituitary ta chykinins, but ovariectomy and estrogen administration failed to significan tly affect tachykinin concentrations in the anterior pituitary of transgeni c mice. Tachykinin immunostaining was detected in some somatotropes, but ta chykinins were also present in cells that were not GH positive. These findi ngs indicate that hyperstimulated somatotropes contain increased stores of tachykinins and that these cells are a source of tachykinins in the anterio r pituitary. Tachykinin stores in the anterior pituitary of transgenic mice were affected by thyroid hormones but seem to be insensitive to estrogens. The GHRH transgenic mice may be an interesting model to study the regulati on of tachykinin stores in the anterior pituitary gland.