5α-Dihydroprogesterone (5α-DHP) is a progesterone receptor agonist and metabolite of progesterone .1 It is formed from progesterone by 5α-reductase.2 It induces gene expression mediated by the progesterone receptor (PR) in reporter assays using HepG2 cells expressing equine PR or human PR (EC50s = 14 and 23.1 nM, respectively).1 5α-DHP (0.7 mg/kg) maintains equine pregnancy in the absence of luteal progesterone. It increases proliferation of C4HD murine mammary cells when used at a concentration of 1 ?M and induces tumor formation in a C4HD mouse model of tumorigenesis in a dose-dependent manner.3 5α-DHP levels increase locally following spinal cord injury or traumatic brain injury in rats and ischemic brain injury in mice.2
1.Scholtz, E.L., Krishnan, S., Ball, B.A., et al.Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesteroneProc. Natl. Acad. Sci. USA111(9)3365-3370(2014) 2.Guennoun, R., Labombarda, F., Gonzalez Deniselle, M.C., et al.Progesterone and allopregnanolone in the central nervous system: Response to injury and implication for neuroprotectionJ. Steroid Biochem. Mol. Biol.14648-61(2015) 3.Wiebe, J.P., Rivas, M.A., Mercogliano, M.F., et al.Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasterideJ. Steroid Biochem. Mol. Biol.14927-34(2015)