Article ID: EJ26-0148
The meibomian glands play a central role in maintaining ocular surface homeostasis by producing meibum, which is the lipid layer of the tear film that suppresses tear evaporation. Dysregulation of the secretion of this lipid leads to meibomian gland dysfunction (MGD), the most common cause of evaporative dry eye disease. Accumulating evidence indicates that androgen signaling is a critical regulator of meibomian gland structure and function. In contrast to classical endocrine mechanisms, androgen action in this tissue is largely mediated by intracrine steroid metabolism, whereby circulating adrenal precursors are locally converted to active androgens within the gland. Key steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), are expressed in the meibomian acinar cells, thereby enabling local testosterone production. Simultaneously, the gland exhibits robust metabolic pathways that convert testosterone to downstream androstane derivatives, providing a mechanism for the spatially restricted control of androgen signaling. Recent study has revealed that the intracrine steroidogenic system is affected by circadian rhythms. In particular, 3β-HSD activity exhibits daily rhythmicity that parallels fluctuations in nicotinamide adenine dinucleotide (NAD+), suggesting that NAD+-dependent metabolic processes contribute to temporal control of local androgen production. Importantly, administration of NAD+ precursors improves meibomian gland morphology in experimental models of aging-associated MGD. This review summarizes the current knowledge on intracrine androgen metabolism in the meibomian gland and highlights emerging metabolic and circadian mechanisms that may provide novel therapeutic targets for dry eye disease.
