Neurotransmitter modulation of the GHRH-GH axis.

GARCIA TORNADU I; RISSO,G; PEREZ-MILLÁN, MI; NOAIN,D; DIAZ TORGA G; LOW,MJ; RUBINSTEIN M; BECU-VILLALOBOS, D.

Frontiers of Hormone Research

Kargers

Año: 2008

The role of dopaminergic receptors in the control of GH release remains controversial. The dopamine receptor2 (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 was a significant decrease in somatotrope population, which was paralleled by decreased GH content and output from pituitary cells. The sensitivity of GHRH-induced GH and cAMP release was similar between genotypes, even though the response amplitude was 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 expression were 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 that might lead 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, MUPS and growth retard.