Gene therapy in the neuroendocrine system.
The implementation of experimental gene therapy in animal models of neuroendocrine diseases is an area of growing interest. In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively, were stereotaxically injected in the relevant hypothalamic regions. In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons, which are involved in the tonic inhibitory control of prolactin secretion and lactotropic cell proliferation. Stereotaxic injection of an adenoviral vector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia and restored TIDA neuron numbers. Spontaneous intermediate lobe pituitary tumors in a retinoblastoma (Rb) gene mutant mouse were corrected by injection of an adenoviral vector expressing the human Rb cDNA and experimental prolactinomas in rats were partially reduced by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidine kinase suicide gene. These results suggest that further implementation of gene therapy strategies in neuroendocrine models may be highly rewarding.
Hereñú
C B
CB
Institute for Biochemical Research-Histology B, Faculty of Medicine, National University of La Plata, La Plata, Argentina.
Morel
G R
GR
Bellini
M J
MJ
Reggiani
P C
PC
Sosa
Y E
YE
Brown
O A
OA
Goya
R G
RG
D000375:Aging / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D004700:Endocrine System Diseases / Q000628:therapy*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics; D009490:Neurosecretory Systems; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000628:therapy; D051381:Rats; D011910:Rats, Brattleboro; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D012175:Retinoblastoma / Q000235:genetics
D050505:Mutant Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin