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Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice.
- Source :
-
Endocrinology [Endocrinology] 2002 Apr; Vol. 143 (4), pp. 1270-9. - Publication Year :
- 2002
-
Abstract
- We determined the consequences of the loss of D2 receptors (D2R) on the GH-IGF-I axis using mice deficient in functional dopamine D2 receptors by targeted mutagenesis (D2R(-/-)). Body weights were similar at birth, but somatic growth was less in male D2R(-/-) mice from 1-8 months of age and in D2R(-/-) females during the first 2 months. The rate of skeletal maturation, as indexed by femur length, and the weight of the liver and white adipose tissue were decreased in knockout male mice even though food intake was not altered. The serum GH concentration was significantly decreased during the first 2 months in knockout female and male mice, and IGF-I and IGF-binding protein-3 levels were lower in knockout mice. PRL was significantly higher in knockout mice, and females attained higher levels than males. Pituitaries from adult knockout mice had impaired basal GH release and a lower response to GHRH in vitro. We propose that the D2R participates in GHRH/GH release in the first month of life. In accordance, the D2R antagonist sulpiride lowered GH levels in 1-month-old wild-type mice. Our results indicate that lack of D2R alters the GHRH-GH-IGF-I axis, and impairs body growth and the somatotrope population.
- Subjects :
- Animals
Body Weight genetics
Body Weight physiology
Cells, Cultured
Dopamine Antagonists pharmacology
Dopamine D2 Receptor Antagonists
Eating genetics
Female
Growth genetics
Growth physiology
Growth Hormone blood
Insulin-Like Growth Factor Binding Protein 3 metabolism
Male
Mice
Mice, Knockout
Prolactin blood
Radioimmunoassay
Receptors, Dopamine D1 antagonists & inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Stress, Psychological genetics
Stress, Psychological metabolism
Dwarfism genetics
Growth Hormone metabolism
Insulin-Like Growth Factor I metabolism
Receptors, Dopamine D2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 143
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 11897683
- Full Text :
- https://doi.org/10.1210/endo.143.4.8750