madman
Super Moderator
* 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.
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 localconversion/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 3a/3b-ketosteroid reductase expression. We therefore reinforce theidea that androgens are metabolically inactivated within the glands. These metabolite markers may help toassess meibomian local androgen activity using meibum.
Collectively, in the present study, we have elucidated the molecular identity of the tissue-endogenous androgen metabolismin the meibomian gland. The deactivation of active steroid hormones is equally important as their de novo synthesis in determining the time and space of their actions. Our studies contribute to understanding the intracrine system of the meibomian gland, encompassing both the generation and deactivationof local steroid hormones. Our methods used in this study and results/findings may pave the way to understand the local steroid-hormone system reported in other intracrine tissues.
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 localconversion/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 3a/3b-ketosteroid reductase expression. We therefore reinforce theidea that androgens are metabolically inactivated within the glands. These metabolite markers may help toassess meibomian local androgen activity using meibum.
Collectively, in the present study, we have elucidated the molecular identity of the tissue-endogenous androgen metabolismin the meibomian gland. The deactivation of active steroid hormones is equally important as their de novo synthesis in determining the time and space of their actions. Our studies contribute to understanding the intracrine system of the meibomian gland, encompassing both the generation and deactivationof local steroid hormones. Our methods used in this study and results/findings may pave the way to understand the local steroid-hormone system reported in other intracrine tissues.
