Research Article| Volume 55, SUPPLEMENT 1, S75-S82, November 01, 2006

Inhibition of 5α-reductase in the rat prostate by Cimicifuga racemosa



      Prostate cancers and many thereof derived cell lines, as the LNCaP cells, grow androgen-dependent. In vivo testosterone is locally converted by 5α-reductase to 5α-dihydrotestosterone (5α-DHT) which is the major androgenic principle in prostates and seminal vesicles. The occurrence of prostate cancer and growth of LNCaP cells can be effectively inhibited by finasteride, a synthetic 5α-reductase inhibitor and by a black cohosh (Cimicifuga racemosa, CR) extract. In the present contribution we tested whether the aqueous/ethanolic C. racemosa extract BNO 1055 contains 5α-reductase inhibitors.


      Immature 24-day-old male rats were fed with testosterone (T)-containing food and injected with 30 mg CR BNO 1055 or 0.5 mg finasteride for 5 days. Average daily T-uptake was 39 mg/animal. Other animals remained untreated or received vehicle injections only.


      In comparison to totally untreated rats the testosterone treatment increased weight of prostates and seminal vesicles 3–5-fold and this proliferation was largely and equipotently inhibited by finasteride and CR BNO 1055. 5α-Dihydrotestosterone concentrations in prostate tissue extracts were also reduced by both compounds and the testosterone-upregulated androgen receptor and insulin like growth factor I gene expression inhibited in the seminals vesicles.


      Taken together, these results indicate that the CR extract BNO 1055 contains one or more potent 5α-reductase inhibitors which may make this extract suitable for the prevention and treatment of prostate cancer and possibly of benign prostate hyperplasia (BPH).


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        • Andriole G.
        • Bostwick D.
        • Brawley O.
        • et al.
        Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.
        J Urol. 2004; 172: 1314-1317
        • Andriole G.
        • Bruchovsky N.
        • Chung L.W.
        • et al.
        Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia.
        J Urol. 2004; 172: 1399-1403
        • Borst S.E.
        • Lee J.H.
        • Conover C.F.
        Inhibition of 5{alpha}-reductase blocks prostate effects of testosterone without blocking anabolic effects.
        Am J Physiol Endocrinol Metab. 2005; 288: E222-E227
        • Flores E.
        • Bratoeff E.
        • Cabeza M.
        • Ramirez E.
        • Quiroz A.
        • Heuze I.
        Steroid 5alpha-reductase inhibitors.
        Mini Rev Med Chem. 2003; 3: 225-237
        • Chen W.
        • Thiboutot D.
        • Zouboulis C.C.
        Cutaneous androgen metabolism: basic research and clinical perspectives.
        J Invest Dermatol. 2002; 119: 992-1007
        • Kaufman K.D.
        Androgens and alopecia.
        Mol Cell Endocrinol. 2002; 198: 89-95
        • Gao W.
        • Kearbey J.D.
        • Nair V.A.
        • et al.
        Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia.
        Endocrinology. 2004; 145: 5420-5428
        • Handratta V.D.
        • Jelovac D.
        • Long B.J.
        • et al.
        Potent CYP17 inhibitors: improved syntheses, pharmacokinetics and anti-tumor activity in the LNCaP human prostate cancer model.
        J Steroid Biochem Mol Biol. 2004; 92: 155-165
        • Higgins B.
        • Thompson I.M.
        The prostate cancer prevention trial: current status.
        J Urol. 2004; 171 (discussion S18): S15-S17
        • Klein E.A.
        • Thompson I.M.
        Update on chemoprevention of prostate cancer.
        Curr Opin Urol. 2004; 14: 143-149
        • Marberger M.
        • Adolfsson J.
        • Borkowski A.
        • et al.
        The clinical implications of the prostate cancer prevention trial.
        BJU Int. 2003; 92: 667-671
        • Thomas L.N.
        • Lazier C.B.
        • Gupta R.
        • et al.
        Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer.
        Prostate. 2004; 15: 231-239
        • Thompson I.M.
        • Goodman P.J.
        • Tangen C.M.
        • et al.
        The influence of finasteride on the development of prostate cancer.
        N Engl J Med. 2003; 349: 215-224
        • Wang L.G.
        • Mencher S.K.
        • McCarron J.P.
        • Ferrari A.C.
        The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: case report and review.
        Oncol Rep. 2004; 11: 1325-1329
        • Lowe F.C.
        • McConnell J.D.
        • Hudson P.B.
        • et al.
        Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.
        Urology. 2003; 61: 791-796
        • Jarry H.
        • Thelen P.
        • Christoffel V.
        • Spengler B.
        • Wuttke W.
        Cimicifuga racemosa extract BNO 1055 inhibits proliferation of the human prostate cancer cell line LNCaP.
        Phytomedicine. 2005; 12: 178-182
        • Seidlova-Wuttke D.
        • Jarry H.
        • Pitzel L.
        • Wuttke W.
        Effects of estradiol-17ß, testosterone and a black cohosh preparation on bone and prostate in orchidectomized rats.
        Maturitas. 2005; 51: 187-198
        • Heinlein C.A.
        • Chang C.
        Androgen receptor in prostate cancer.
        Endocr Rev. 2004; 25: 276-308
        • Kuiper G.G.
        • Enmark E.
        • Pelto-Huikko M.
        • Nilsson S.
        • Gustafsson J.A.
        Cloning of a novel receptor expressed in rat prostate and ovary.
        Proc Natl Acad Sci USA. 1996; 93: 5925-5930
        • Weihua Z.
        • Lathe R.
        • Warner M.
        • Gustafsson J.A.
        An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta, 17beta-diol, and CYP7B1, regulates prostate growth.
        Proc Natl Acad Sci USA. 2002; 99: 13589-13594
        • Weihua Z.
        • Warner M.
        • Gustafsson J.A.
        Estrogen receptor beta in the prostate.
        Mol Cell Endocrinol. 2002; 193: 1-5
        • Imamov O.
        • Morani A.
        • Shim G.J.
        • et al.
        Estrogen receptor beta regulates epithelial cellular differentiation in the mouse ventral prostate.
        Proc Natl Acad Sci USA. 2004; 101: 9375-9380
        • Heinlein C.A.
        • Chang C.
        Androgen receptor (AR) coregulators: an overview.
        Endocr Rev. 2002; 23: 175-200
        • Risbridger G.P.
        • Bianco J.J.
        • Ellem S.J.
        • McPherson S.J.
        Oestrogens and prostate cancer.
        Endocr Relat Cancer. 2003; 10: 187-191
        • Gray Jr., L.E.
        • Ostby J.
        • Wilson V.
        • et al.
        Xenoendocrine disrupters-tiered screening and testing: filling key data gaps.
        Toxicology. 2002; 181–182: 371-382
        • Gelbke H.P.
        • Kayser M.
        • Poole A.
        OECD test strategies and methods for endocrine disruptors.
        Toxicology. 2004; 205: 17-25
        • Rosen M.B.
        • Wilson V.S.
        • Schmid J.E.
        • Gray L.E.
        Gene expression analysis in the ventral prostate of rats exposed to vinclozolin or procymidone.
        Reprod Toxicol. 2005; 19: 367-379
        • Nellemann C.
        • Dalgaard M.
        • Holst B.
        • Bonefeld-Jorgensen E.C.
        • Vinggaard A.M.
        Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor.
        Mol Cell Endocrinol. 2005; 237: 25-35
        • Seidlova-Wuttke D.
        • Jarry H.
        • Pitzel L.
        • Wuttke W.
        Effects of estradiol-17ß, testosterone and a black cohosh preparation on bone and prostate in orchidectomized rats.
        Maturitas. 2005; 51: 177-186
        • Popp M.
        • Schenk R.
        • Abel G.
        Cultivation of Cimicifuga racemosa (L.) nuttal and quality of CR extract BNO 1055.
        Maturitas. 2003; 44: S1-S7
        • Wright A.S.
        • Douglas R.C.
        • Thomas L.N.
        • Lazier C.B.
        • Rittmaster R.S.
        Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alpha-reductase.
        Endocrinology. 1999; 140: 4509-4515
        • Fitts J.M.
        • Klein R.M.
        • Powers C.A.
        Comparison of tamoxifen and testosterone propionate in male rats: differential prevention of orchidectomy effects on sex organs, bone mass, growth, and the growth hormone-IGF-I axis.
        J Androl. 2004; 25: 523-534
        • Torring N.
        • Vinter-Jensen L.
        • Pedersen S.B.
        • Sorensen F.B.
        • Flyvbjerg A.
        • Nexo E.
        Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate.
        J Urol. 1997; 158: 222-227
        • Yeap B.B.
        • Wilce J.A.
        • Leedman P.J.
        The androgen receptor mRNA.
        Bioessays. 2004; 26: 672-682
        • Lau K.M.
        • LaSpina M.
        • Long J.
        • Ho S.M.
        Expression of estrogen receptor (ER)-alpha and ER-beta in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth regulation.
        Cancer Res. 2000; 60: 3175-3182
        • Liu J.
        • Burdette J.E.
        • Xu H.
        • et al.
        Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms.
        J Agric Food Chem. 2001; 49: 2472-2479
        • Zierau O.
        • Bodinet C.
        • Kolba S.
        • Wulf M.
        • Vollmer G.
        Antiestrogenic activities of Cimicifuga racemosa extracts.
        J Steroid Biochem Mol Biol. 2002; 80: 125-130
        • Wober J.
        • Heinrich K.
        • Scheel B.
        • Vollmer G.
        Phytoestrogens effects in a human endometrial adenocarcinoma cell line using an estrogen receptor ß (ERß) transactivation system. Paper presented at: the 51st Annual Congress of the Society for Medicinal Plant Research.
        Kiel, Germany2003
        • Brunnberg S.
        • Pettersson K.
        • Rydin E.
        • Matthews J.
        • Hanberg A.
        • Pongratz I.
        The basic helix-loop-helix-PAS protein ARNT functions as a potent coactivator of estrogen receptor-dependent transcription.
        Proc Natl Acad Sci USA. 2003; 100: 6517-6522
        • Safe S.
        • Wormke M.
        • Samudio I.
        Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in human breast cancer cells.
        J Mammary Gland Biol Neoplasia. 2000; 5: 295-306
        • Schoenfeld J.R.
        • Vasser M.
        • Jhurani P.
        • et al.
        Distinct molecular phenotypes in murine cardiac muscle development, growth, and hypertrophy.
        J Mol Cell Cardiol. 1998; 30: 2269-2280
        • Chang C.S.
        • Kokontis J.
        • Liao S.T.
        Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors.
        Proc Natl Acad Sci USA. 1988; 85: 7211-7215