INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Neurotransmitter Modulation of the
Autor/es:
GARCÍA-TORNADÚ I; RISSO, G.; PEREZ-MILLÁN, M.I.; NOAIN D; DIAZ-TORGA, G; LOW MJ; RUBINSTEIN M; BECU-VILLALOBOS D
Revista:
Frontiers of Hormone Reseach
Editorial:
Karger
Referencias:
Año: 2010 vol. 38 p. 59 - 69
ISSN:
0301-3073
Resumen:
The role of dopaminergic receptors in the control of GH release remains controversial. The dopamine
receptor 2 (D2R) knockout mouse represents a useful model to study the participation of the D2R on
growth and GHRH-GH regulation. These knockout mice have hyperprolactinemia and lactotrope
hyperplasia, but unexpectedly, they are also growth retarded. In D2R knockout mice there is a significant
decrease in somatotrope population, which is paralleled by decreased GH content and output
from pituitary cells. The sensitivity of GHRH-induced GH and cAMP release is similar between
genotypes, even though the response amplitude is lower in knockouts. We point to an involvement
of D2R signaling at the hypothalamic level as dopamine did not release GH acting at the pituitary
level, and both somatostatin and GHRH mRNA expression are altered in knockout mice. The similarity
of the pituitary defect in the D2R knockout mouse to that of GHRH deficient models suggests a
probable mechanism. Loss of dopamine signaling via hypothalamic D2Rs at a critical age may cause
inadequate GHRH secretion subsequently leading to inappropriate somatotrope lineage development.
Furthermore, GH pulsatility, which depends on a regulated temporal balance between GHRH
and somatostatin output might be compromised in D2R knockout mice, leading to lower IGF-I, and
growth retardation.