Basic and Translational Science Effect of a Hypercholesterolemic Diet on Serum Lipid Profile, Plasma Sex Steroid Levels, and Prostate Structure in Rats Katherine Ploumidou, Aspasia Kyroudi-Voulgari, Despina Perea, Ioannis Anastasiou, and Dionisios Mitropoulos OBJECTIVES The purpose of this study was to examine the impact of a hypercholesterolemic diet (HD) on serum lipid profile, plasma sex steroid levels, and ventral prostate structure in rats. METHODS Beginning at 120 days of age, male Wistar rats were fed for 5 months with either standard rat chow (15 animals) or standard chow enriched with 4% cholesterol and 1% cholic acid (15 animals). The body and ventral prostate weights (VPWs), plasma sex steroid levels, and lipid profiles were determined, and prostate morphology in fixed tissue sections were studied. RESULTS The body weight of rats fed with HD did not differ from that of controls. However, both absolute and relative VPWs of HD animals were significantly lower than those of controls. HD resulted in significant elevation in total serum cholesterol and LDL levels, whereas HDL and triglyceride levels were comparable. Plasma total testosterone and estriol levels did not differ between groups, but their free fraction, along with sex hormone– binding globulin levels, were significantly affected. HD also affected the microscopic structure of the ventral prostate. Epithelial cells of the distal area formed papillary projections within the acinar lumen and had more cytoplasm than controls. In most cases, vesicular formations within the cytoplasmic area were also noted. CONCLUSIONS Hypercholesterolemia causes marked changes in the ventral prostate, serum lipid profile, and plasma sex steroid profile in rats and possibly alters prostate morphology by affecting the sex steroid axis, thus contributing to prostatic disease pathogenesis. UROLOGY 76: 1517.e1–1517.e5, 2010. © 2010 Elsevier Inc. B enign prostatic hyperplasia (BPH) is the most common benign disease in men over 40 years of age, resulting from proliferation of stromal and glandular elements. 1 The development and progression of BPH appears to depend on a complex interaction of cellular, hereditary, endocrine, and environmental fac- tors, especially lifestyle and nutrition. 2-4 Dietary and nu- tritional factors may have a causal effect on prostate disease through a variety of mechanisms such as alter- ations in androgen and estrogen levels 5 and sympathetic nervous system activity. 6 Results obtained from experiments with laboratory an- imals indicate that there is a connection between fat intake and alterations in prostate structure and func- tion. 7-9 The effect of dietary fat on sex hormones is controversial. In men, a high-fat, low-fiber diet does not influence plasma sex hormone levels (except for the sex hormone– binding globulin (SHBG)– bound testosterone fraction, which is significantly higher) but alters endogenous metabolism of sex hormones, resulting in higher daily uri- nary excretion of testosterone and lower daily urinary ex- cretion of estradiol and estrone. 5 In rats, a high-fat diet does not significantly influence levels of serum and intraprostatic androgens or expression of androgen response genes. 8 How- ever, other investigators have reported impaired testicular function and lower plasma androgen levels in rats with diet-induced hypercholesterolemia. 10,11 An understanding of the mechanisms by which hyper- cholesterolemia influences the normal prostate in vivo may eventually provide insights into the role of the diet in the pathogenesis and management of prostatic diseases such as BPH or even prostate cancer. The present study evaluated the influence of a hypercholesterolemic diet (HD) on serum lipid profile, serum levels of sex steroid hormones, and ventral prostate structure in the rat. MATERIAL AND METHODS Thirty normal male Wistar rats were purchased from the Pas- teur Institute in Athens. Upon arrival, the rats were randomly segregated into groups of three that were housed in individual plastic cages with wood chip bedding in a controlled environ- From the Laboratory of Experimental Surgery and Surgical Research, Athens Medical School, Athens, Greece; Department of Histology and Embryology, Athens Medical School, Athens, Greece; and First Department of Urology, Athens Medical School, Athens, Greece Reprint requests: Katherine Ploumidou, R.D., M.D., Ph.D., Laboratory of Exper- imental Surgery and Surgical Research, Athens Medical School, Ag. Thoma 15b Goudi 11572, Athens, Greece. E-mail: catplou@yahoo.gr © 2010 Elsevier Inc. 0090-4295/10/$36.00 1517.e1 All Rights Reserved doi:10.1016/j.urology.2010.07.515