Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas
Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of...
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todo:paper_09477349_v108_n3_p202_PaezPereda2023-10-03T15:49:31Z Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas Páez Pereda, M. Lohrer, P. Kovalovsky, D. Perez Castro, C. Goldberg, V. Losa, M. Chervín, A. Berner, S. Molina, H. Stalla, G.K. Renner, U. Arzt, E. ACTH Corticotroph adenoma Interleukin-6 Proopiomelanocortin corticotropin dexamethasone interleukin 6 proopiomelanocortin adult article clinical article controlled study cytokine release female gene expression hormone release human human cell human tissue hypophysis tumor male priority journal Adenoma Adrenocorticotropic Hormone Adult Cushing Syndrome Female Gene Expression Regulation, Neoplastic Humans Interleukin-6 Male Middle Aged Pituitary Neoplasms Pro-Opiomelanocortin Recombinant Proteins RNA, Messenger Transcription, Genetic Tumor Cells, Cultured Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene expression in corticotroph adenoma cell cultures. This first demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL-6 production by corticotroph adenoma cells and in addition, demonstrated for the first time that the synthetic glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6 production. This intratumoral produced IL-6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Cushing's disease. However, elevated glucocorticoid levels in patients with Cushing's disease may prevent excessive action of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo. Fil:Páez Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kovalovsky, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Perez Castro, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09477349_v108_n3_p202_PaezPereda |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
ACTH Corticotroph adenoma Interleukin-6 Proopiomelanocortin corticotropin dexamethasone interleukin 6 proopiomelanocortin adult article clinical article controlled study cytokine release female gene expression hormone release human human cell human tissue hypophysis tumor male priority journal Adenoma Adrenocorticotropic Hormone Adult Cushing Syndrome Female Gene Expression Regulation, Neoplastic Humans Interleukin-6 Male Middle Aged Pituitary Neoplasms Pro-Opiomelanocortin Recombinant Proteins RNA, Messenger Transcription, Genetic Tumor Cells, Cultured |
| spellingShingle |
ACTH Corticotroph adenoma Interleukin-6 Proopiomelanocortin corticotropin dexamethasone interleukin 6 proopiomelanocortin adult article clinical article controlled study cytokine release female gene expression hormone release human human cell human tissue hypophysis tumor male priority journal Adenoma Adrenocorticotropic Hormone Adult Cushing Syndrome Female Gene Expression Regulation, Neoplastic Humans Interleukin-6 Male Middle Aged Pituitary Neoplasms Pro-Opiomelanocortin Recombinant Proteins RNA, Messenger Transcription, Genetic Tumor Cells, Cultured Páez Pereda, M. Lohrer, P. Kovalovsky, D. Perez Castro, C. Goldberg, V. Losa, M. Chervín, A. Berner, S. Molina, H. Stalla, G.K. Renner, U. Arzt, E. Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| topic_facet |
ACTH Corticotroph adenoma Interleukin-6 Proopiomelanocortin corticotropin dexamethasone interleukin 6 proopiomelanocortin adult article clinical article controlled study cytokine release female gene expression hormone release human human cell human tissue hypophysis tumor male priority journal Adenoma Adrenocorticotropic Hormone Adult Cushing Syndrome Female Gene Expression Regulation, Neoplastic Humans Interleukin-6 Male Middle Aged Pituitary Neoplasms Pro-Opiomelanocortin Recombinant Proteins RNA, Messenger Transcription, Genetic Tumor Cells, Cultured |
| description |
Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene expression in corticotroph adenoma cell cultures. This first demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL-6 production by corticotroph adenoma cells and in addition, demonstrated for the first time that the synthetic glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6 production. This intratumoral produced IL-6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Cushing's disease. However, elevated glucocorticoid levels in patients with Cushing's disease may prevent excessive action of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo. |
| format |
JOUR |
| author |
Páez Pereda, M. Lohrer, P. Kovalovsky, D. Perez Castro, C. Goldberg, V. Losa, M. Chervín, A. Berner, S. Molina, H. Stalla, G.K. Renner, U. Arzt, E. |
| author_facet |
Páez Pereda, M. Lohrer, P. Kovalovsky, D. Perez Castro, C. Goldberg, V. Losa, M. Chervín, A. Berner, S. Molina, H. Stalla, G.K. Renner, U. Arzt, E. |
| author_sort |
Páez Pereda, M. |
| title |
Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| title_short |
Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| title_full |
Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| title_fullStr |
Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| title_full_unstemmed |
Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas |
| title_sort |
interleukin-6 is inhibited by glucocorticoids and stimulates acth secretion and pomc expression in human corticotroph pituitary adenomas |
| url |
http://hdl.handle.net/20.500.12110/paper_09477349_v108_n3_p202_PaezPereda |
| work_keys_str_mv |
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