INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE ANTERIOR-PITUITARY GLAND - INDUCTION BY INTERFERON-GAMMA IN A SUBPOPULATION OF FOLLICULOSTELLATE CELLS AND IN AN UNIDENTIFIABLE POPULATION OF NON-HORMONE-SECRETING CELLS

In the context of immune-endocrine relationships, we have previously s hown that interferon-gamma (IFN-gamma) inhibits hormone secretion in a nterior pituitary (AP) cell cultures. The non-hormone-secreting follic ulostellate (FS) cells were found to mediate this inhibitory action. B ecause in the immune system IFN-gamma is a strong stimulator of nitric oxide (NO) release through the induction of NO synthase (NOS), we inv estigated whether the inducible form of NOS (iNOS) is present in (rat) AP cell cultures, and whether its expression is stimulated by IFN-gam ma. Immunocytochemistry revealed that under basal in vitro conditions only a very few AP cells contained iNOS. Treatment with IFN-gamma caus ed a sixfold rise in the number of iNOS-positive cells and augmented t he intensity of the staining. The increased number of iNOS-expressing cells was paralleled by elevated production of NO. Some of the iNOS-po sitive cells extended cytoplasmic processes between hormone-secreting cells, which is a characteristic of FS cells. Immunostaining of FS cel l-poor and FS cell-enriched populations (obtained by gradient sediment ation) also suggested the presence of iNOS in a subpopulation of FS ce lls. By double immunofluorescence techniques we found that about 65% o f iNOS-expressing cells were positive for S-100, a marker protein for FS cells. However, around 80% of the S-100-positive cells were not lab eled for iNOS. On the other hand, the majority of the S-100-negative i NOS-containing cells could not be further identified by antisera again st the classical AP hormones, suggesting the presence of iNOS in a sti ll unidentified non-hormone-secreting cell type of the AP gland. This report is the first to demonstrate the expression of the inducible for m of NOS in the AP gland. IFN-gamma upregulates this expression, showi ng that cytokines may use the same signaling mechanisms in both the im mune and the endocrine system. In addition, a putative new function of a subpopulation of FS cells in the paracrine regulation of the AP gla nd is suggested.