Journal of Steroid Biochemistry & Molecular Biology 92 (2004) 435–446 Altered testicular microsomal steroidogenic enzyme activities in rats with lifetime exposure to soy isoflavones Mark J. McVey a,b , Gerard M. Cooke a,b,∗ , Ivan H.A. Curran b a Department of Cellular and Molecular Medicine and Obstetrics and Gynecology, Reproductive Biology Unit, University of Ottawa, Ont., Canada b Toxicology Research Division, Health Products and Foods Branch, Food Directorate, Health Canada, 2202D1 Tunney’s Pasture, Ottawa, Ont., Canada K1A 0L2 Received 6 May 2004; accepted 26 August 2004 Abstract Androgen production in the testis is carried out by the Leydig cells, which convert cholesterol into androgens. Previously, isoflavones have been shown to affect serum androgen levels and steroidogenic enzyme activities. In this study, the effects of lifelong exposure to dietary soy isoflavones on testicular microsomal steroidogenic enzyme activities were examined in the rat. F1 male rats were obtained from a multi-generational study where the parental generation was fed diets containing alcohol-washed soy protein supplemented with increasing amounts of Novasoy, a commercially available isoflavone supplement. A control group was maintained on a soy-free casein protein-based diet (AIN93G). The diets were designed to approximate human consumption levels and ranged from 0 to 1046.6 mg isoflavones/kg pelleted feed, encompassing exposures representative of North American and Asian diets as well as infant fed soy-based formula. Activities of testicular 3-hydroxysteroid dehydrogenase (3-HSD), P450c17 (CYP17), 17-hydroxysteroid dehydrogenase (17-HSD) were assayed on post natal day (PND) 28, 70, 120, 240 and 360 while 5-reducatase was assayed on PND 28. At PND 28, 3-HSD activity was elevated by approximately 50% in rats receiving 1046.6 mg total isoflavones/kg feed compared to those on the casein only diet. A similar increase in activity was observed for CYP17 in rats receiving 235.6mg total isoflavones/kg feed, a level representative of infant exposure through formula, compared to those receiving 0 mg isoflavones from the casein diet. These results demonstrate that rats fed a mixture of dietary soy isoflavones showed significantly altered enzyme activity profiles during development at PND 28 as a result of early exposure to isoflavones at levels obtainable by humans. © 2004 Elsevier Ltd. All rights reserved. Keywords: 3-HSD; CYP17; Testicular enzyme activity; Soy isoflavones 1. Introduction Many plants contain phytoestrogens, a class of compounds that have estrogenic properties and appear to function in anti- fungal defence [1,2]. Isoflavones are a type of phytoestrogen found in foods such as legumes, lentils and chickpeas. Soy foods such as soybeans, soy milk products, soy flour and soy-based infant formulas [3,4] have the highest recorded levels of isoflavones in food, and as such represent a large source of dietary isoflavones [3,5]. Human consumption of soy is on the rise as more soy based foods and supplements ∗ Corresponding author. Tel.:+1 613 957 0990; fax: +1 613 941 6959. E-mail address: Gerard Cooke@hc-sc.gc.ca (G.M. Cooke). are becoming available and vegetarianism grows in popu- larity. Published benefits of soy isoflavones include thera- peutic value for hormone replacement therapy in menopause as well as antioxidant and antipromotional effects against coronary heart disease, various cancers and osteoporosis [1,6–10]. Research examining possible deleterious effects of phy- toestrogens began during the 1940s, following the discovery that consumption of plants rich in phytoestrogens caused an- imals to abort their fetuses [11]. Some animal studies exam- ining the safety of isoflavone consumption have not shown impairment of male sperm production or reproductive tract development [12,13], while other studies have shown dele- terious effects in terms of reproductive success and health 0960-0760/$ – see front matter © 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.jsbmb.2004.08.002