Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity
Summary: Intracrinology—wherein hormones are synthesized in the organ where they exert their effect without release into circulation—has been described. However, molecular mechanisms of hormone deactivation within intracrine tissue are still largely unknown. The meibomian glands in the eyelids produ...
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000689 |
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| author | Khanh Tien Nguyen Pham Takahito Miyake Tomo Suzuki Shigeru Kinoshita Yuki Hamada Hikari Uehara Mamiko Machida Takeshi Nakajima Emi Hasegawa Masao Doi |
| author_facet | Khanh Tien Nguyen Pham Takahito Miyake Tomo Suzuki Shigeru Kinoshita Yuki Hamada Hikari Uehara Mamiko Machida Takeshi Nakajima Emi Hasegawa Masao Doi |
| author_sort | Khanh Tien Nguyen Pham |
| collection | DOAJ |
| description | Summary: Intracrinology—wherein hormones are synthesized in the organ where they exert their effect without release into circulation—has been described. However, molecular mechanisms of hormone deactivation within intracrine tissue are still largely unknown. The meibomian glands in the eyelids produce oil (meibum) to the ocular surface to prevent dehydration (dry eye). Androgens are generated inside this gland and are crucial for its tissue-homeostasis. However, there is no data showing the presence of androgens in meibum, implying local conversion/deactivation into unknown metabolites. Here, we performed radioactive tracer studies in combination with pharmacological enzyme inhibition, followed by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and found three androgen metabolites—androstanedione, androsterone, and epiandrosterone—in mouse and human meibomian glands. Accounting for the enzymatic conversion, we show tissue-endogenous 3α/3β-ketosteroid reductase expression. We therefore reinforce the idea that androgens are metabolically inactivated within the glands. These metabolite markers may help to assess meibomian local androgen activity using meibum. |
| format | Article |
| id | doaj-art-86e3718cc450416ba58d649039c0b4a8 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-86e3718cc450416ba58d649039c0b4a82025-02-07T04:48:02ZengElsevieriScience2589-00422025-02-01282111808Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activityKhanh Tien Nguyen Pham0Takahito Miyake1Tomo Suzuki2Shigeru Kinoshita3Yuki Hamada4Hikari Uehara5Mamiko Machida6Takeshi Nakajima7Emi Hasegawa8Masao Doi9Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, JapanDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, JapanDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Kamigyō-ku, Kyoto 602-0841, Japan; Department of Ophthalmology, Kyoto City Hospital, Nakagyō-ku, Kyoto 604-8845, JapanDepartment of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kamigyō-ku, Kyoto 602-0841, JapanDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, JapanDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, JapanSenju Laboratory of Ocular Sciences, Senju Pharmaceutical Co., Ltd., Kobe 650-0047, JapanSenju Laboratory of Ocular Sciences, Senju Pharmaceutical Co., Ltd., Kobe 650-0047, JapanDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, JapanDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan; Corresponding authorSummary: Intracrinology—wherein hormones are synthesized in the organ where they exert their effect without release into circulation—has been described. However, molecular mechanisms of hormone deactivation within intracrine tissue are still largely unknown. The meibomian glands in the eyelids produce oil (meibum) to the ocular surface to prevent dehydration (dry eye). Androgens are generated inside this gland and are crucial for its tissue-homeostasis. However, there is no data showing the presence of androgens in meibum, implying local conversion/deactivation into unknown metabolites. Here, we performed radioactive tracer studies in combination with pharmacological enzyme inhibition, followed by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and found three androgen metabolites—androstanedione, androsterone, and epiandrosterone—in mouse and human meibomian glands. Accounting for the enzymatic conversion, we show tissue-endogenous 3α/3β-ketosteroid reductase expression. We therefore reinforce the idea that androgens are metabolically inactivated within the glands. These metabolite markers may help to assess meibomian local androgen activity using meibum.http://www.sciencedirect.com/science/article/pii/S2589004225000689BiochemistryMolecular BiologyPhysiology |
| spellingShingle | Khanh Tien Nguyen Pham Takahito Miyake Tomo Suzuki Shigeru Kinoshita Yuki Hamada Hikari Uehara Mamiko Machida Takeshi Nakajima Emi Hasegawa Masao Doi Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity iScience Biochemistry Molecular Biology Physiology |
| title | Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity |
| title_full | Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity |
| title_fullStr | Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity |
| title_full_unstemmed | Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity |
| title_short | Identification of meibomian gland testosterone metabolites produced by tissue-intrinsic intracrine deactivation activity |
| title_sort | identification of meibomian gland testosterone metabolites produced by tissue intrinsic intracrine deactivation activity |
| topic | Biochemistry Molecular Biology Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000689 |
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