Differential Activity of 2-Methylene-19-Nor Vitamin D Analogs on Growth Factor Gene Expression in Rhino Mouse Skin and Comparison to All-Trans Retinoic Acid

The study found that while all tested 2-methylene-19-nor analogs of vitamin D3 increased epidermal thickness in rhino mice, only some reduced utricle size, a process known as comedolysis, similar to the effects of all-trans retinoic acid (atRA). Specifically, the analog 2MbisP was more effective at increasing epidermal thickness rapidly compared to atRA, and both reduced utricle area at the same rate. However, 2MbisP uniquely increased the expression of amphiregulin and epigen mRNA without affecting other epidermal growth factor receptor (EGFR) ligands or the EGFR itself. Another analog, CAGE-3, thickened the epidermis but did not reduce utricle size or significantly affect AREG mRNA levels. These findings suggest that 2MbisP's ability to alter specific EGFR ligand mRNAs may contribute to its effects on epidermal proliferation and comedolysis.