A dominant phenocopy of hypopituitarism in transgenic mice resulting from central nervous system synthesis of human growth hormone

Abstract

We have produced a line of transgenic mice in which expression of human GH has been detected only in the cerebral cortex. Both male and female transgenic mice are growth inhibited with respect to their nontransgenic littermates. Mouse GH mRNA and insulin-like growth factor-I mRNA levels in the pituitary and liver, respectively, are reduced, and circulating insulin-like growth factor-I levels are lower in these mice. Within the hypothalamus somatostatin mRNA levels are increased and GH-releasing factor mRNA levels are reduced compared to those in nontransgenic littermates. We suggest that the growth retardation in these mice is a consequence of the ectopic human GH disturbing the normal controls that regulate mouse GH synthesis and release from the pituitary. These mice provide a resource for analysis of the regulation of GH production and demonstrate that a dominant phenocopy can be made by producing transgenic mice that have local production of an extra-cellular hormone.