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Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response of anterior pituitary cells

Marianela Candolfi1, Gabriela Jaita, Verónica Zaldivar

  • 1Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Neuroendocrinology
|October 12, 2004
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) alters nitric oxide synthase (NOS) expression in pituitary cells. While upregulating inducible NOS (iNOS), it downregulates estrogen-induced endothelial NOS (eNOS), revealing NO

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) influences anterior pituitary cell proliferation and apoptosis in an estrogen-dependent manner.
  • Nitric oxide (NO) has been shown to mediate the inhibitory effects of TNF-alpha on prolactin release.

Purpose of the Study:

  • To investigate the impact of TNF-alpha on nitric oxide synthase (NOS) activity and expression in anterior pituitary cells.
  • To elucidate the role of NO in TNF-alpha-induced apoptosis of anterior pituitary cells.

Main Methods:

  • Assessing NOS activity and expression (iNOS, eNOS, nNOS) in anterior pituitary cells from rats at different estrous cycle stages and ovariectomized (OVX) rats.
  • Utilizing 17beta-estradiol (E2) and NOS inhibitors (NAME, NMMA) to study NO's role in TNF-alpha-induced apoptosis.

Main Results:

  • TNF-alpha stimulated NOS activity and upregulated inducible NOS (iNOS) gene expression in anterior pituitary cells.
  • TNF-alpha downregulated estrogen-induced endothelial NOS (eNOS) expression, while E2 stimulated eNOS expression.
  • NOS inhibitors were required for TNF-alpha to induce apoptosis, and NO appeared to restrain TNF-alpha's proapoptotic effect.

Conclusions:

  • TNF-alpha modulates NOS expression by upregulating iNOS and downregulating E2-induced eNOS in anterior pituitary cells.
  • Endogenous NO may play a restraining role, rather than a mediating role, in TNF-alpha-induced apoptosis of anterior pituitary cells.

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