Targeted deletion of somatotroph insulin-like growth factor-I signaling in a cell-specific knockout mouse model

Christopher J. Romero, Yewade Ng, Raul M. Luque, Rhonda D. Kineman, Linda Koch, Jens C. Bruning, Sally Radovick

Research output: Contribution to journalArticle

Abstract

The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I remain unclear. We have developed a cell-specific knockout mouse in which the IGF-I receptor was ablated from the somatotroph in order to validate and characterize IGF-I negative regulation; we termed this the somatotroph IGF-I receptor knockout (SIGFRKO) mouse. The SIGFRKO mice demonstrated increased GH gene expression and secretion as well as increased serum IGF-I. Compensatory changes were noted with decreased GHRH and increased somatostatin mRNA expression levels. SIGFRKO mice had normal linear growth, but by 14 wk of age weighed significantly less than controls. Furthermore, metabolic studies revealed SIGFRKO mice had significantly less fat mass and body percent fat. These data support somatotroph IGF-I negative regulation and suggest that hypothalamic feedback limits the extent of GH release. The SIGFRKO mouse is a model delineating the mechanisms of IGF-I regulation in the hypothalamic- pituitary axis and demonstrates compensatory mechanisms that mediate growth and metabolic function in mammals.

Original languageEnglish (US)
Pages (from-to)1077-1089
Number of pages13
JournalMolecular Endocrinology
Volume24
Issue number5
DOIs
StatePublished - May 1 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Romero, C. J., Ng, Y., Luque, R. M., Kineman, R. D., Koch, L., Bruning, J. C., & Radovick, S. (2010). Targeted deletion of somatotroph insulin-like growth factor-I signaling in a cell-specific knockout mouse model. Molecular Endocrinology, 24(5), 1077-1089. https://doi.org/10.1210/me.2009-0393