| First Author | Sasaki L | Year | 2022 |
| Journal | Nat Aging | Volume | 2 |
| Issue | 2 | Pages | 105-114 |
| PubMed ID | 37117756 | Mgi Jnum | J:347048 |
| Mgi Id | MGI:7520733 | Doi | 10.1038/s43587-021-00167-8 |
| Citation | Sasaki L, et al. (2022) Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction. Nat Aging 2(2):105-114 |
| abstractText | Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD(+))-dependent circadian 3beta-hydroxyl-steroid dehydrogenase (3beta-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3beta-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3beta-HSD activity by boosting its coenzyme NAD(+) availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3beta-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction. |
