11β-Hydroxysteroid dehydrogenase type 1 (HSD11β1) is an NADPH-dependent enzyme. In particular, 11β-HSD isozymes are tissue-specific regulators of Glucocorticoid (GC) pre-receptor metabolism. Obviously, it consists of hsd11β1 and hsd111β2 composition. HSD11β1 is mainly used as an oxidoreductase to convert inactive cortisone into active cortisol. Particularly, HSD11β2 is also an effective dehydrogenase, which can convert cortisol into inactive metabolite cortisone. Importantly, HSD11β is highly expressed in liver and adipose tissue and also distributed in skeletal muscle, vascular smooth muscle, central nervous system, eye, synovium, and bone.

Interestingly, HSD11β1 is a negative regulator of keratinocyte and fibroblast proliferation. Specifically, the activity of HSD11β in fibroblasts increased with age. This means HSD11βplays a role in the morphological changes of aging skin. HSD11β1 in regulating GC mediated effects on sebocyte function. Here, we will introduce a competitive HSD11β1 inhibitor, Adrenosterone.

Adrenosterone, a Steroid Hormone, is a Competitive HSD11β1 Inhibitor.

Above all, Adrenosterone is a steroid hormone with a weak androgenic effect. Besides, Adrenosterone is a dietary supplement that can decrease fat and increase muscle mass. Moreover, Adrenosterone acts as a suppressor of metastatic progression of human cancer cells

Secondly, Adrenosterone markedly decreases Snail and Slug expression in HCCLM3 and MDA-MB-231 cells. Furthermore, Adrenosterone suppresses cell motility and invasion of highly metastatic human cancer cells (HCCLM3, MDA-MB-231, and MDA-MB-435 cells). At the same time, Adrenosterone-treated cells did not show decreased expression of mesenchymal makers such as N-cadherin and vimentin.

Once again, Adrenosterone causes cells to recover epithelial traits. By the way, the percentage of E-cadherin–positive cells (E-cad⁺ cells) in Adrenosterone-treated HCCLM3 is ∼30%.

All in all, Adrenosterone is a competitive HSD11β1 inhibitor.

References:

Joji Nakayama, et al. Mol Cancer Res. 2020 Mar;18(3):477-487.