J. steroid Biochem. Vol. 30, No. 1-6, pp. 395-399, 1988 00X2-4731/88 $3.00+0.00 Printed in Great Britain Pergamon Press plc zyxwvut EFFECTS OF TWO DIFFERENT MEDICAL TREATMENTS ON DIHYDROTESTOSTERONE CONTENT AND ANDROGEN RECEPTORS IN HUMAN BENIGN PROSTATIC HYPERPLASIA E. PETWGELI*, F. SCIARRA, F. DI SILVERIO~, V. TOSCANO, C. LUBRANO, C. CONTI and G. CONCOLINO Istituto di Clinica Medica V, tlstituto di Patologia Urologica, Universita “La Sapienza”, Rome 00161, Italy Summary-In order to evaluate the biochemical modifications induced by hormonal treatments on human prostatic tissue, the intracellular distribution of tissue DHT and AR were investigated in BPH patients untreated and treated (25-30 days before surgery) with the association of cyproterone acetate (CPA), 100 mg p.o./day plus tamoxifen (TAM), 100 mg p.o./day, or with flutamide (FLU) alone, 750 mg p.o./day. Dexrran-coated charcoal and exchange assay in the presence of sodium molybdates (0.2 M) were used for AR determination, employing methyltrienolone as radioligand in the presence of triamcinolone acetonide. Endogenous DHT was measured by RIA, after ether extraction and purification on celite microcolumns. The treatment with CPA plus TAM led to a detection of cytosol AR (ARC) in 50% of the specimens, while nuclear AR (ARn) were never measurable. The FLU treatment did not modify the incidence of ARC, while ARn was not detectable. The cytosolic and nuclear compartmentalization of DHT was scarcely affected by the combined CPA plus TAM treatment, while FLU treatment induced a prevalent cytosolic localization of DHT (DHTc=283.2?24.6 S.E. and DHTn= 1138.4k98.7 SE. pg/mg DNA in untreated patients; DHTc= 350.4 k 97.7 SE. and DHTn= 589.7 f 154.4 S.E. pg/mg DNA in CPA plus TAM treated patients; DHTc= 1101.7k 165.7 S.E. and DHTn=733.0?93.9 SE. pgjmg DNA in FLU treated patients). Both medical treatments, therefore, were able to reduce prostatic growth on account of the reduced value of nuclear DHT content. INTRODUCTION The growth of normal and diseased prostate in both animals and humans is regulated by the testicular hormones. Today it is generally accepted that BPH is a focal disease, affected by 17P-estradiol acting on the mesenchymal part of the gland and by DHT on the stromal and epithelial cells [ 11.Human prostate carci- noma is an androgen-dependent epithelial cell dis- ease [2]. Both these prostatic diseases improve with androgen deprivation [3-61. Attempts of medical treatment of prostatic disease have been made with drugs able to induce hormonal modifications in blood as well as in prostatic tissue and to interfere with androgen metabolism at target tissue level. Some of these treatments include the combination of antioestrogen plus antiandro- gen [6, 71, the use of aromatase inhibitors [8], and the administration of antiandrogens alone [9]. Tamoxifen (TAM), a compound which binds to antioestrogen binding sites, able to interfere with oestrogen receptor (ER), has been given in association with the antiandrogen cyproterone acetate (CPA), a steroid compound with progestational and therefore Proceedings of the 8th International Symposium of The Journal of Steroid Biochemistry “Recent Advances in Steroid Biochemistry” (Paris, 24-27 May 1987). *To whom correspondence should be addressed. antigonadotropic effects, which compete with andro- gens for their binding sites. Flutamide (FLU), a pure antiandrogen, able to compete with androgens for androgen receptors AR and to inhibit protein synthesis induced by DHT, has been used without administering other drugs. Androgens exert their action at tissue level through high affinity binding to the specific receptors and the interaction of the activated steroid-receptor complex with the chromatin [ 10-121. Although recent studies have advanced serious doubts whether soluble cytoplasmic steroid receptors (SR) are a biological reality or an artefact of cell disruption [ 13-151, the biochemical determination of both cytosolic and nuclear SR may have an important meaning. Nuclear SR, in fact, are strongly bound to nuclear acceptors, while the cytosolic SR could represent the form not yet transformed or bound with lower affinity to the chromatin. In this regard, the buffer composition affects the AR subcellular distribution, presumably during the homogenization procedure, as previously reported by our group [ 161. In order to better clarify the relationship between hormonal target tissue modifications and the hor- monal treatment used, the subcellular distribution of DHT and its receptor have been evaluated in surgical specimens obtained from BPH patients untreated or treated with different endocrine therapies: (1) the simultaneous administration of an antioestro- 395