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Adenosine A 2A Receptor Gene Disruption Provokes Marked Changes in Melanocortin Content and Pro‐Opiomelanocortin Gene Expression
Author(s) -
Jégou S.,
Yacoubi M. El,
Mounien L.,
Ledent C.,
Parmentier M.,
Costentin J.,
Vaugeois J. M.,
Vaudry H.
Publication year - 2003
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2003.01116.x
Subject(s) - medicine , endocrinology , pars intermedia , hypothalamus , anterior pituitary , melanocortin , biology , pituitary gland , receptor , adenosine a2a receptor , amygdala , chemistry , hormone , adenosine receptor , agonist
Abstract A 2A receptor knockout (A 2A R −/− ) mice are more anxious and aggressive, and exhibit reduced exploratory activity than their wild‐type littermates (A 2A R +/+ ). Because α‐melanocyte‐stimulating hormone (α‐MSH) influences anxiety, aggressiveness and motor activity, we investigated the effect of A 2A R gene disruption on α‐MSH content in discrete brain regions and pro‐opiomelanocortin (POMC) expression in the hypothalamus and pituitary. No modification in α‐MSH content was observed in the hypothalamus and medulla oblongata where POMC‐expressing perikarya are located. In the arcuate nucleus of the hypothalamus, POMC mRNA levels were not affected by A 2A R disruption. Conversely, in A 2A R −/− mice, a significant increase in α‐MSH content was observed in the amygdala and cerebral cortex, two regions that are innervated by POMC terminals. In the pars intermedia of the pituitary, A 2A R disruption provoked a significant reduction of POMC mRNA expression associated with a decrease in α‐MSH content. By contrast, in the anterior lobe of the pituitary, a substantial increase in POMC mRNA and adrenocorticotropin hormone concentrations was observed, and plasma corticosterone concentration was significantly higher in A 2A R −/− mice, revealing hyperactivity of their pituitary‐adrenocortical axis. Together, these results suggest that adenosine, acting through A 2A receptors, may modulate the release of α‐MSH in the cerebral cortex and amygdala. The data also indicate that A 2A receptors are involved in the control of POMC gene expression and biosynthesis of POMC‐derived peptides in pituitary melanotrophs and corticotrophs.