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Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response of anterior pituitary cells.
Neuroendocrinology. 2004; 80(2):83-91.N

Abstract

We previously reported that tumor necrosis factor-alpha (TNF-alpha) inhibits cell proliferation whereas it stimulates apoptosis of anterior pituitary cells in an estrogen-dependent manner. Also, we showed that nitric oxide (NO) mediates the inhibitory effect of TNF-alpha on prolactin release. Here, we studied the effect of TNF-alpha on nitric oxide synthase (NOS) activity and expression in anterior pituitary cells from cycling and ovariectomized (OVX) rats, and the role of NO in TNF-alpha induced apoptosis of anterior pituitary cells. NOS activity was higher in anterior pituitary cells from rats in proestrus than in diestrus and was stimulated by 17beta-estradiol (10(-9) M, E2). TNF-alpha (50 ng/ml) stimulated NOS activity in anterior pituitary cells from rats at both stages of the estrous cycle and in cells from OVX rats cultured either with or without E2. Inducible NOS (iNOS) gene expression was higher in anterior pituitary cells from rats in proestrus than in diestrus and its expression was enhanced by TNF-alpha. Acute administration of E2 to OVX rats increased endothelial NOS (eNOS) expression in the anterior pituitary gland. Also, E2 increased eNOS mRNA in dispersed anterior pituitary cells from OVX rats, and this effect was blocked by TNF-alpha. nNOS expression in the anterior pituitary gland was higher at proestrus than at diestrus but eNOS expression was similar at both stages. TNF-alpha decreased eNOS mRNA in anterior pituitary cells from rats at proestrus or diestrus. In anterior pituitary cells from OVX rats, TNF-alpha failed to induce apoptosis but was able to induce it when cells were incubated with NAME or NMMA, NOS inhibitors that did not affect cell viability per se. In the presence of E2, NAME induced apoptosis and enhanced the proapoptotic effect of TNF-alpha. In conclusion, our study shows that TNF-alpha upregulates iNOS gene expression whereas it downregulates estrogen-induced eNOS expression in anterior pituitary cells. Endogenous NO may restrain rather than mediate the proapoptotic effect of TNF-alpha in anterior pituitary cells.

Authors+Show Affiliations

Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15475661

Citation

Candolfi, Marianela, et al. "Tumor Necrosis Factor-alpha-induced Nitric Oxide Restrains the Apoptotic Response of Anterior Pituitary Cells." Neuroendocrinology, vol. 80, no. 2, 2004, pp. 83-91.
Candolfi M, Jaita G, Zaldivar V, et al. Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response of anterior pituitary cells. Neuroendocrinology. 2004;80(2):83-91.
Candolfi, M., Jaita, G., Zaldivar, V., Zárate, S., Pisera, D., & Seilicovich, A. (2004). Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response of anterior pituitary cells. Neuroendocrinology, 80(2), 83-91.
Candolfi M, et al. Tumor Necrosis Factor-alpha-induced Nitric Oxide Restrains the Apoptotic Response of Anterior Pituitary Cells. Neuroendocrinology. 2004;80(2):83-91. PubMed PMID: 15475661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response of anterior pituitary cells. AU - Candolfi,Marianela, AU - Jaita,Gabriela, AU - Zaldivar,Verónica, AU - Zárate,Sandra, AU - Pisera,Daniel, AU - Seilicovich,Adriana, Y1 - 2004/10/06/ PY - 2004/04/01/received PY - 2004/07/23/accepted PY - 2004/10/12/pubmed PY - 2005/1/14/medline PY - 2004/10/12/entrez SP - 83 EP - 91 JF - Neuroendocrinology JO - Neuroendocrinology VL - 80 IS - 2 N2 - We previously reported that tumor necrosis factor-alpha (TNF-alpha) inhibits cell proliferation whereas it stimulates apoptosis of anterior pituitary cells in an estrogen-dependent manner. Also, we showed that nitric oxide (NO) mediates the inhibitory effect of TNF-alpha on prolactin release. Here, we studied the effect of TNF-alpha on nitric oxide synthase (NOS) activity and expression in anterior pituitary cells from cycling and ovariectomized (OVX) rats, and the role of NO in TNF-alpha induced apoptosis of anterior pituitary cells. NOS activity was higher in anterior pituitary cells from rats in proestrus than in diestrus and was stimulated by 17beta-estradiol (10(-9) M, E2). TNF-alpha (50 ng/ml) stimulated NOS activity in anterior pituitary cells from rats at both stages of the estrous cycle and in cells from OVX rats cultured either with or without E2. Inducible NOS (iNOS) gene expression was higher in anterior pituitary cells from rats in proestrus than in diestrus and its expression was enhanced by TNF-alpha. Acute administration of E2 to OVX rats increased endothelial NOS (eNOS) expression in the anterior pituitary gland. Also, E2 increased eNOS mRNA in dispersed anterior pituitary cells from OVX rats, and this effect was blocked by TNF-alpha. nNOS expression in the anterior pituitary gland was higher at proestrus than at diestrus but eNOS expression was similar at both stages. TNF-alpha decreased eNOS mRNA in anterior pituitary cells from rats at proestrus or diestrus. In anterior pituitary cells from OVX rats, TNF-alpha failed to induce apoptosis but was able to induce it when cells were incubated with NAME or NMMA, NOS inhibitors that did not affect cell viability per se. In the presence of E2, NAME induced apoptosis and enhanced the proapoptotic effect of TNF-alpha. In conclusion, our study shows that TNF-alpha upregulates iNOS gene expression whereas it downregulates estrogen-induced eNOS expression in anterior pituitary cells. Endogenous NO may restrain rather than mediate the proapoptotic effect of TNF-alpha in anterior pituitary cells. SN - 0028-3835 UR - https://www.unboundmedicine.com/medline/citation/15475661/Tumor_necrosis_factor_alpha_induced_nitric_oxide_restrains_the_apoptotic_response_of_anterior_pituitary_cells_ L2 - https://www.karger.com?DOI=10.1159/000081313 DB - PRIME DP - Unbound Medicine ER -