Gene therapy in the neuroendocrine system

HEREÑÚ CB; MOREL GR,; BELLINI MJ; REGGIANI PC; SOSA YE; BROWN OA; GOYA RG

FRONTIERS OF HORMONE RESEARCH.

Karger

Lugar: Basel, Suiza; Año: 2006 vol. 35 p. 135 - 142

0301-3073

The implementation of experimental gene therapy in animal models of neuroendocrinediseases is an area of growing interest. In the hypothalamus, restorative gene therapy hasbeen successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutantwhich suffers from diabetes insipidus, and in Koletsky (fak/fak) and in Zucker (fa/fa) ratswhich have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic.In the above models, viral vectors expressing AVP, leptin receptor b and proopiomeolanocortin,respectively, were stereotaxically injected in the relevant hypothalamic regions.In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibulardopaminergic (TIDA) neurons, which are involved in the tonic inhibitory controlof prolactin secretion and lactotropic cell proliferation. Stereotaxic injection of an adenoviralvector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia andrestored TIDA neuron numbers. Spontaneous intermediate lobe pituitary tumors in aretinoblastoma (Rb) gene mutant mouse were corrected by injection of an adenoviral vectorexpressing the human Rb cDNA and experimental prolactinomas in rats were partiallyreduced by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidinekinase suicide gene. These results suggest that further implementation of gene therapy strategiesin neuroendocrine models may be highly rewarding.