Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks

Tanaka
In: International Journal of Molecular Medicine · 2009 · vol. 23(3) , pp. 421–8 · doi:10.3892/ijmm_00000147 · PMID:19212662 · W1979368191
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Danazol enhances endometrial stromal cell decidualization by modulating endometrial cytokine networks, influencing functional subpopulation ratios rather than acting like progesterone.

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Tanaka (2009) studied the direct in vitro effects of danazol on normal human endometrial stromal cell (ESC) subpopulations, using decidualization assays with or without 8Br-cAMP stimulation to evaluate cell viability, PRL secretion, and cytokine (G-CSF and IL-8) responses. Danazol did not change viable cell numbers in unstimulated or 8Br-cAMP–decidualized ESCs, but dose-dependently increased viable cell numbers during decidualization, induced ESC decidualization similarly to progesterone/MPA, and synergistically enhanced decidual differentiation. Although progesterone and medroxyprogesterone acetate increased G-CSF and IL-8 secretion, danazol did not and instead completely inhibited the 8Br-cAMP–induced increases in G-CSF and IL-8 secretion. The limitation is that findings are based on normal ESCs in vitro rather than on endometriotic tissue or in vivo mechanisms. This paper is centrally about endometriosis — it investigates danazol’s direct cellular actions on endometrial stromal cells in the context of proposed mechanisms for improving endometriotic signs and symptoms.

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Abstract

Local danazol therapy can improve endometriotic signs and symptoms without causing any menstrual disorders. As a consequence, certain direct actions of danazol on endometriotic tissues have been proposed, but the mechanisms of these actions have not been clarified. In the present study, the direct effects of danazol on normal human endometrial stromal cells (ESCs) were examined using in vitro decidualization assays. Danazol did not affect the viable cell numbers of unstimulated ESCs or 8Br-cAMP-stimulated decidualized ESCs, but significantly enhanced the viable cell numbers of 8-Br-cAMP-stimulated ESCs during decidualization in a dose-dependent manner. Danazol had no effect on PRL secretion by 8-Br-cAMP-stimulated decidualized ESCs. Danazol, as well as progesterone and medroxyprogesterone acetate (MPA), induced ESC decidualization. Danazol synergistically enhanced the differentiation process of 8-Br-cAMP-stimulated ESCs during decidualization. Although progesterone and MPA increased G-CSF and IL-8 secretion by ESCs in similar manner to 8-Br-cAMP, danazol had no such effects. Moreover, remarkable increases in G-CSF and IL-8 secretions by 8-Br-cAMP-stimulated ESCs during decidualization were completely inhibited by cotreatment with danazol. These results indicate that danazol has specific pharmacological effects on ESCs, rather than progesterone-like effects or similar effects to those reported for endometrial cytokines. According to the results, normal human ESCs can be classified into at least four functional subpopulations. Therefore, under certain circumstances, danazol has similar or opposite effects on ESCs to certain endometrial cytokines, suggesting that it regulates functional cellular subpopulation ratios of normal human ESCs by modifying the endometrial cytokine network in endometrial stromal tissues.
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Print ISSN: 1107-3756 Online ISSN: 1791-244X International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease. International Journal of Oncology is an international journal devoted to oncology research and cancer treatment. Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery. Oncology Reports is an international journal devoted to fundamental and applied research in Oncology. Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine. Oncology Letters is an international journal devoted to Experimental and Clinical Oncology. Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology. International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis. Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology. Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition. Publishes open-access research on using epigenetics to advance understanding and treatment of human disease. An International Open Access Journal Devoted to General Medicine. Article - Authors: - Pages: 421-428|Published online on: March 1, 2009https://doi.org/10.3892/ijmm_00000147 - Expand metrics + Local danazol therapy can improve endometriotic signs and symptoms without causing any menstrual disorders. As a consequence, certain direct actions of danazol on endometriotic tissues have been proposed, but the mechanisms of these actions have not been clarified. In the present study, the direct effects of danazol on normal human endometrial stromal cells (ESCs) were examined using in vitro decidualization assays. Danazol did not affect the viable cell numbers of unstimulated ESCs or 8Br-cAMP-stimulated decidualized ESCs, but significantly enhanced the viable cell numbers of 8-Br-cAMP-stimulated ESCs during decidualization in a dose-dependent manner. Danazol had no effect on PRL secretion by 8-Br-cAMP-stimulated decidualized ESCs. Danazol, as well as progesterone and medroxyprogesterone acetate (MPA), induced ESC decidualization. Danazol synergistically enhanced the differentiation process of 8-Br-cAMP-stimulated ESCs during decidualization. Although progesterone and MPA increased G-CSF and IL-8 secretion by ESCs in similar manner to 8-Br-cAMP, danazol had no such effects. Moreover, remarkable increases in G-CSF and IL-8 secretions by 8-Br-cAMP-stimulated ESCs during decidualization were completely inhibited by cotreatment with danazol. These results indicate that danazol has specific pharmacological effects on ESCs, rather than progesterone-like effects or similar effects to those reported for endometrial cytokines. According to the results, normal human ESCs can be classified into at least four functional subpopulations. Therefore, under certain circumstances, danazol has similar or opposite effects on ESCs to certain endometrial cytokines, suggesting that it regulates functional cellular subpopulation ratios of normal human ESCs by modifying the endometrial cytokine network in endometrial stromal tissues. Copy and paste a formatted citation Spandidos Publications style Tanaka T: Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks. Int J Mol Med 23: 421-428, 2009. APA Tanaka, T. (2009). Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks. International Journal of Molecular Medicine, 23, 421-428. https://doi.org/10.3892/ijmm_00000147 MLA Tanaka, T."Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks". International Journal of Molecular Medicine 23.3 (2009): 421-428. Chicago Tanaka, T."Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks". International Journal of Molecular Medicine 23, no. 3 (2009): 421-428. https://doi.org/10.3892/ijmm_00000147

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