Signal transduction of gonadotropin-releasing hormone-induced gonadotropin subunit and growth hormone gene expression in the goldfish pituitary
Best known for its regulation of the production and secretion of pituitary gonadotropin hormones (GtHs), gonadotropin-releasing hormone (GnRH) is the central regulator of reproduction in all vertebrates. In mammalian and non-mammalian systems, the signaling pathways mediating GnRH-induced GtH and growth hormone (GH, fish only) secretion have been extensively studied. In contrast, much less is known about the mechanisms mediating GnRH-induced GtH subunit gene expression, especially in nonmammalian vertebrates. Moreover, the signaling pathways coupling GnRH receptor activation to increases in GH gene expression have not been investigated in any model system. The purpose of the present study was to investigate the signal transduction pathways that mediate GnRH-induced increases in GtH subunit and GH mRNA levels, with emphasis on the roles of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). The main hypothesis of this study was that the two native GnRHs use similar signal transduction pathways coupling GnRH receptors to GtH subunit and GH gene expression and release in the goldfish pituitary. Initial experiments revealed significant differences in the time- and dose-related effects of the two GnRHs in vivo and in vitro. Studies were then carried out to investigate the role of PKC in GnRH-induced GtH and GH gene expression in goldfish pituitary cells. Western blot analysis confirmed the presence of conventional, novel and atypical PK Cs in the goldfish pituitary. The results presented in this dissertation suggest a dual role for PKC in the regulation of GtH, but not GH, gene expression. Moreover, the data would appear to refute the hypothesis that conventional and novel PKCs are involved in GnRH-induced GtH and GH gene expression. The involvement of the ERK pathway in GnRH-stimulated GtH and GH gene expression was demonstrated using a combination of Northern and Western blot analysis. Although GnRH-induced GtH and GH gene expression is ERK-dependent, the data suggest a PKC-independent mechanism of activation. Together these results provide novel insights into the complexity and functional-specificity of GnRH signaling with respect to the regulation of secretion and gene expression in gonadotropes and somatotropes.
Bibliography: p. 129-145
Klausen, C. (2004). Signal transduction of gonadotropin-releasing hormone-induced gonadotropin subunit and growth hormone gene expression in the goldfish pituitary (Unpublished doctoral thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/17619