Lack of neuronal NOS has consequences for the expression of POMC and POMC-derived peptides in the mouse pituitary

The relevance of NO in neuroendocrine signalling has been investigated by a nalysis of cellular expression of pro-opiomelanocortin (POMC) and the POMC- derived peptides beta -endorphin, alpha -melanocyte stimulating hormone and adrenocorticotropin. Expression patterns were studied in the pituitary gla nd of 150-day old wild-type and neuronal-NOS (nNOS) knock-out mice by using immunohistochemistry, in situ hybridization and Northern blot analysis. Re maining NO-generating capacities in the knock-out mice were demonstrated by immunohistochemical localization of inducible, endothelial and neuronal NO S isoforms. Quantitative analysis revealed that cellular expression of POW mRNA was drastically reduced in the pituitary of knock-out mice in comparis on to controls. In situ hybridization studies demonstrated that this reduct ion was most pronounced in the intermediate lobe, while the anterior lobe w as much less affected. Immunostaining for the proteolytic fragments of POW was significantly reduced in the intermediate lobe cells of knock-out mice. A moderate reduction of immunostaining for these peptides was also observe d in adenopituitary cells of nNOS knock-out mice. Our data demonstrate that the lack of nNOS substantially affects cellular levels of pituitary opioid peptides, which may have consequences for the response of these animals to stress and pain.