Neurotransmitter modulation of the GHRH-GH axis.
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.
García-Tornadu
Isabel
I
Risso
Gabriela
G
Perez-Millan
Maria Ines
MI
Noain
Daniela
D
Diaz-Torga
Graciela
G
Low
Malcolm J
MJ
Rubinstein
Marcelo
M
Becu-Villalobos
Damasia
D
D000172:Acromegaly / Q000188:drug therapy; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006128:Growth; D013006:Growth Hormone / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D006801:Humans; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology
D018377:Neurotransmitter Agents; D017448:Receptors, Dopamine D2; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D004298:Dopamine