Transcriptional Control of Adrenal Steroidogenesis
| Autor: | Anne-Marie Lefrançois-Martinez, Nadine Binart, Antonine Blondet-Trichard, Jean-Christophe Pointud, Isabelle Sahut-Barnola, Céline Chambon, Antoine Martinez, Pierre Val |
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| Přispěvatelé: | Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2011 |
| Předmět: |
endocrine system
medicine.medical_specialty 030209 endocrinology & metabolism [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] CREB Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Corticosterone Internal medicine medicine Cyclic AMP Response Element-Binding Protein Protein kinase A Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Janus kinase 2 biology Adrenal cortex Tyrosine phosphorylation Cell Biology Endocrinology medicine.anatomical_structure chemistry biology.protein Janus kinase hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, 286 (38), pp.32976-32985. ⟨10.1074/jbc.M111.218016⟩ Journal of Biological Chemistry, 2011, 286 (38), pp.32976-32985. ⟨10.1074/jbc.M111.218016⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | In the adrenal gland, adrenocorticotropin (ACTH) acting through the cAMP protein kinase (PKA) transduction pathway is the main regulator of genes involved in glucocorticoid synthesis. The prolactin (PRL) receptor is expressed in the adrenal cortex of most mammals, but experimental proof that PRL ensures direct control on glucocorticoid synthesis in rodents remains elusive. To unravel the physiological importance of PRL in adrenocortical functions, we measured steroidogenic capacity of Prlr-deficient mice (Prlr−/−) and explored the influence of JAK/STAT signaling, the major PRL transduction pathway, on the steroidogenic activity of adrenocortical cell cultures. We demonstrate that lack of Prlr does not affect basal (nor stress-induced) corticosterone levels in mice. PRL triggers JAK2/STAT5-dependent transcription in adrenal cells, but this does not influence corticosterone release. In contrast, pharmacological or siRNA-mediated inhibition of JAK2 reveals its essential role in both basal and ACTH/cAMP-induced steroidogenesis. We demonstrate that nuclear JAK2 regulates the amount of active transcription factor CREB (cAMP response element-binding protein) through tyrosine phosphorylation and prevention of proteasomal degradation, which in turn leads to transcriptional activation of the rate-limiting steroidogenic Star gene. Hence, we describe a novel link between PKA and JAK2 by which nuclear JAK2 signaling controls adrenal steroidogenesis by increasing the stability of CREB. |
| Databáze: | OpenAIRE |
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