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| Kofi... |
 Posted: Tue Nov 03, 2009 6:12 am |
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Neuropeptides. 2009 Aug;43(4):267-74. Epub 2009 Jun 30.
Hypothalamic orexin, OX1, alphaMSH, NPY and MCRs expression in
dopaminergic D2R knockout mice.
Garcia-Tornadu I, Diaz-Torga G, Risso GS, Silveyra P, Cataldi N, Ramirez
MC, Low MJ, Libertun C, Becu-Villalobos D.
Instituto de Biologia y Medicina Experimental, Consejo Nacional de
Investigaciones Cientificas y Tecnicas, V. Obligado 2490, 1428 Buenos
Aires, Argentina.
In 5-month-old male and female dopamine receptor 2 (D2R) knockout mice
food intake per animal was unaltered while food per g BW was increased.
We wished to evaluate the effect of D2R disruption on different
components of energy balance and food intake regulation. We determined
hypothalamic orexin precursor (PPO) expression, its receptor OX1, serum
leptin levels, hypothalamic leptin receptor (OBR), circulating and
pituitary alpha MSH levels, as well as central MC3 and MC4 receptors and
NPY mRNA in wildtype and D2R knockout mice (KO). Loss of D2R caused a
marked increase in serum prolactin levels, to higher levels in females
compared to male KO mice. On the other hand, it produced a
female-specific increase in circulating alphaMSH, and hypothalamic
alphaMSH content, while neurointermediate alphaMSH content was decreased
in both sexes. No differences were found in hypothalamic NPY, MC3R or
MC4R concentration. Hypothalamic PPO mRNA expression was significantly
decreased only in female KOs, while OX1 mRNA was not different between
genotypes. Serum leptin levels were also similar in both genotypes. Our
results show that in female and not in male mice disruption of the D2R
produces two potentially anorexigenic events: an increase in serum and
hypothalamic alphaMSH, and a decrease in hypothalamic orexin expression.
Very high prolactin levels, which are orexigenic, probably
counterbalance these effects, so that food intake is slightly altered.
In males, on the other hand, hypothalamic PPO, and serum or hypothalamic
alphaMSH are not modified, and increased prolactin levels may account
for increased food intake per g BW. These results suggest a sexually
dimorphic participation of the D2R in food intake regulation.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19570576 |
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