Dutasteride

Dutasteride, an oral synthetic 4-azasteroid, is a potent, selective, irreversible inhibitor of type 1 and type 2 5α-reductase (5AR)^[1]. Inhibition of 5AR types 1 and 2 with Dutasteride caused downregulation of 5α-dihydrotestosterone, and results in hepatic insulin resistance, hepatic lipid accumulation, and decreased adipose lipid mobilization^[3]. Dutasteride has been widely used in prostatic hyperplasia research to reduce prostate volume, improve urinary flow and decreased the incidence of acute urinary retention^[3].

In vitro, Dutasteride treatment for 72 hours significantly inhibited the viability of LNCaP and DU145 cells, with IC₅₀ values of 10μM and 40μM, respectively^[4]. Treatment with 5μM Dutasteride for 24 hours reduced the metabolic activity of U87 cells and delayed the invasion^[5]. Incubation with 1µM Dutasteride for 72 hours inhibited progesterone-induced cell detachment of MCF-7 cells and blocked the production of 5AR^[6].

In vivo, Dutasteride treatment via intraperitoneal injection at a dose of 12.5mg/kg/day for 10 consecutive days alleviated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum of mice, and increased homovanillic acid (HVA) content^[7]. Daily oral administration of Dutasteride at a dose of 10mg/kg for 55 consecutive days suppressed prostate cancer progression in R-3327H rats^[8].

References:
[1] Evans H C, Goa K L. Dutasteride[J]. Drugs & aging, 2003, 20(12): 905-916.
[2] Traish A M. Health risks associated with long-term finasteride and dutasteride use: it's time to sound the alarm[J]. The World Journal of Men's Health, 2020, 38(3): 323.
[3] Andriole G L, Kirby R. Safety and tolerability of the dual 5α-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia[J]. European urology, 2003, 44(1): 82-88.
[4] Biancolella M, Valentini A, Minella D, et al. Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines[J]. Investigational new drugs, 2007, 25(5): 491-497.
[5] Orozco M, Valdez R A, Ramos L, et al. Dutasteride combined with androgen receptor antagonists inhibit glioblastoma U87 cell metabolism, proliferation, and invasion capacity: Androgen regulation[J]. Steroids, 2020, 164: 108733.
[6] Wiebe J P, Souter L, Zhang G. Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2006, 100(4-5): 129-140.
[7] Litim N, Morissette M, Caruso D, et al. Effect of the 5α-reductase enzyme inhibitor dutasteride in the brain of intact and parkinsonian mice[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2017, 174: 242-256.
[8] Xu Y, Dalrymple S L, Becker R E, et al. Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers[J]. Clinical Cancer Research, 2006, 12(13): 4072-4079.