Hsd11b1, also known as 11-beta-hydroxysteroid dehydrogenase-1, is an enzyme that converts inert glucocorticoids into active forms in tissues, thus regulating local glucocorticoid levels. Glucocorticoids are potent suppressors of immune responses. Hsd11b1 is involved in multiple biological processes, and its associated pathways include those related to immune regulation, steroidogenesis, and metabolism [1,2]. Genetic models such as gene knockout mice are valuable for studying its functions.

In melanoma, Hsd11b1 expressed in different cellular compartments acts as a negative feedback mechanism in response to T cell immunotherapies. Hsd11b1 inhibitors can improve the response to PD-1 blockade in a CD8+ T cell-dependent manner by augmenting interferon-γ production [1]. In bovine granulosa cells, progesterone modulates Hsd11b1-mediated cortisol production, and progestogens suppress cortisol production by regulating Hsd11b1 expression [2]. In endometriosis, Hsd11b1 is upregulated in ectopic endometrial lesions, which may contribute to the disease by inhibiting dendritic cell proliferation and maturation [3].

In conclusion, Hsd11b1 plays crucial roles in immune regulation, steroidogenesis-related processes, and disease-associated cellular functions. The use of gene knockout mouse models has helped to reveal its functions in diseases such as melanoma, endometriosis, and in understanding the interaction between progesterone and cortisol production. These findings provide insights into potential therapeutic strategies, like repurposing Hsd11b1 inhibitors for melanoma immunotherapy [1].

References:

1. Martins Nascentes Melo, Luiza, Herrera-Rios, Dayana, Hinze, Daniel, Hölzel, Michael, Helfrich, Iris. 2023. Glucocorticoid activation by HSD11B1 limits T cell-driven interferon signaling and response to PD-1 blockade in melanoma. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2021-004150. https://pubmed.ncbi.nlm.nih.gov/37028818/

2. Mukangwa, Memory, Tetsuka, Masafumi. 2023. Progesterone modulates HSD11B1-mediated cortisol production in luteinized bovine granulosa cells. In The Journal of reproduction and development, 69, 206-213. doi:10.1262/jrd.2023-005. https://pubmed.ncbi.nlm.nih.gov/37344443/

3. Yang, Xu, Jiang, Lu, Xu, Yao. 2024. HSD11B1 overexpression in dendritic cells and stromal cells relates to endometriosis by inhibiting dendritic cell proliferation and maturation. In Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 40, 2411607. doi:10.1080/09513590.2024.2411607. https://pubmed.ncbi.nlm.nih.gov/39387602/