Alpha- and beta-melanocyte stimulating hormone positively impact lipogenesis of meibomian gland cells in vitro and ex vivo

Zahn I, Socher E, Bergua A, Schikorra T, Kleinsasser B, Garreis F, Schicht M, Dietrich J, Paulsen F (2025)


Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 185

Pages Range: 117937

Article Number: 117937

DOI: 10.1016/j.biopha.2025.117937

Abstract

Purpose

The meibomian glands produce a lipid-rich secretion that forms the superficial layer of the tear film, preventing excessive evaporation. Dysfunction of these glands (MGD) is the primary cause of dry eye disease (DED), a growing public health concern. Currently, there are limited pharmacological treatments for DED. However, α-/β-melanocyte-stimulating hormones (α-/β-MSH), ligands of the melanocortin receptors (MCR), are known to regulate lipogenesis and differentiation in sebaceous glands. This study investigated the influence of α-/β-MSH on exocrine secretion in human meibomian glands.

Methods

Immunohistochemistry and RT-PCR for MCR expression were performed in human meibomian glands and an immortalized human meibomian gland epithelial cell line (ihMGECs). The effects of α-/β-MSH (agonists) and JNJ-10229570 (antagonist) in ihMGECs on lipid production and MCR response were analyzed using Oil-Red-O staining, transmission electron microscopy, qPCR, and a cAMP assay. Additionally, the effect of α-/β-MSH on an ex vivo organotypic slice culture (OSC) of human eyelids was investigated.

Results

MCR expression was confirmed in human meibomian glands. Stimulation with α-/β-MSH increased cAMP levels and MCR expression. α-/β-MSH dose-dependently induced lipid production in ihMGECs and OSC, resulting in increased lipid droplet formation and upregulation of lipogenesis markers. Co-administration of JNJ-10229570 suppressed this effect.

Conclusion

Our data show for the first time that human meibomian glands express MCRs and that stimulation/inhibition of MCRs alters cAMP response, MCR expression, and lipogenesis markers, thereby affecting the genesis of meibum. Therefore, α-/β-MSH positively impacts meibum production and should be considered in the context of changes in glandular secretion in MGD and potential treatments.

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How to cite

APA:

Zahn, I., Socher, E., Bergua, A., Schikorra, T., Kleinsasser, B., Garreis, F.,... Paulsen, F. (2025). Alpha- and beta-melanocyte stimulating hormone positively impact lipogenesis of meibomian gland cells in vitro and ex vivo. Biomedicine & Pharmacotherapy, 185, 117937. https://doi.org/10.1016/j.biopha.2025.117937

MLA:

Zahn, Ingrid, et al. "Alpha- and beta-melanocyte stimulating hormone positively impact lipogenesis of meibomian gland cells in vitro and ex vivo." Biomedicine & Pharmacotherapy 185 (2025): 117937.

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