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      The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats

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          Abstract

          Purpose Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. Materials and Methods: We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). Results: The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared to C105 (p = 0.0089). Concerning the lumen, surface density presented no difference between C65 and T65 (p = 0.9031) and a decrease of 19% for T105 compared to C105 (p = 0.0061). There was no difference in epithelium surface density between C65 and T65 (p = 0.7375), but it was 51% higher (p = 0.0065) in T105 compared with C105. Regarding stroma surface density, there were no differences between C65 and T65 or between C105 and T105. Finally, there was no difference in collagen pattern between C105 and T105, but T65 showed a predominance of collagen fibers compared to C65. Conclusion: The use of anabolic androgenic steroids in rats promotes structural changes in the prostate. We observed structural changes in the weight, volume and epithelium height of the prostate ventral lobe and a predominance of collagen fibers.

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          A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids.

          Since its discovery in 1935, numerous derivatives of testosterone have been synthesized, with the goals of prolonging its biological activity in vivo, producing orally active androgens, and developing products, commonly referred to as anabolic-androgenic steroids (AAS), that are more anabolic and less androgenic than the parent molecule. This article reviews the structure, biotransformation, and mechanism of action of testosterone and some of the most commonly used AAS. Clinical applications of the AAS are discussed, and guidelines and therapeutic maneuvers for minimizing their side effects are outlined. Literature for inclusion in this review was identified using the libraries of the University of Wisconsin Medical School and School of Pharmacy, the author's files, and searches of MEDLINE, Science Citation Index, Biological Abstracts, and Chemical Abstracts. The myotrophic action of testosterone and its derivatives and their stimulatory effects on the brain have led to widespread use of AAS by athletes and "recreational" drug users. Consequently, all AAS were classified as class III controlled substances in 1991. Nonetheless, AAS have shown benefit in a variety of human disorders, including HIV-related muscle wasting and other catabolic conditions such as chronic obstructive pulmonary disease, severe burn injuries, and alcoholic hepatitis. Because of their diverse biological actions, AAS have been used to treat a variety of other conditions, including bone marrow failure syndromes, constitutional growth retardation in children, and hereditary angioedema. AAS therapy is associated with various side effects that are generally dose related; therefore, illicit use of megadoses of AAS for the purpose of bodybuilding and enhancement of athletic performance can lead to serious and irreversible organ damage. The most common side effects of AAS are some degree of masculinization in women and children, behavioral changes (eg, aggression), hepatotoxicity, and alteration of blood lipid levels and coagulation factors. To minimize or avoid serious toxicities with AAS therapy, close medical supervision and periodic monitoring are important, with dose adjustment as appropriate to achieve the minimum effective dose. Given the biological effects and potential adverse effects of AAS, administration of these agents should be avoided in pregnant women, women with breast cancer or hypercalcemia, men with carcinoma of the prostate or breast, and patients with nephrotic syndromes or significant liver dysfunction.
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            Structural biology of the fibres of the collagenous and elastic systems.

            G Montes (1995)
            The different types of fibres of the collagenous and elastic systems can be demonstrated specifically in tissue sections by comparing the typical ultrastructural picture of each of the fibre types with studies using selective staining techniques for light microscopy. A practical modus operandi, which includes the recommended staining procedures and interpretation of the results, is presented. Micrographs and tables are provided to summarize the differential procedures. Reticulin fibres display a distinct argyrophilia when studied by means of silver impregnation techniques, and show up as a thin meshwork of weakly birefringent, greenish fibres when examined with the aid of the Picrosirius-polarization method. In addition, electron-microscopic studies showed that reticulin fibres are composed of a small number of thin collagen fibrils, contrasting with the very many thicker fibrils that could be localized ultrastructurally to the sites where non-argyrophilic, coarse collagen fibres had been characterized by the histochemical methods used. The three different fibre types of the elastic system belong to a continuous series: oxytalan-elaunin-elastic (all of the fibre types comprising collections of microfibrils with, in the given sequence, increasing amounts of elastin). The three distinct types of elastic system fibres have different staining characteristics and ultrastructural patterns. Ultrastructurally, a characteristic elastic fibre consists of two morphologically different components: a centrally located solid cylinder of amorphous and homogeneous elastin surrounded by tubular microfibrils. An oxytalan fibre is composed of a bundle of microfibrils, identical to the elastic fibre microfibrils, without amorphous material. In elaunin fibres, dispersed amorphous material (elastin) is intermingled among the microfibrils.
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              Endocrine characterization of the designer steroid methyl-1-testosterone: investigations on tissue-specific anabolic-androgenic potency, side effects, and metabolism.

              Various products containing rarely characterized anabolic steroids are nowadays marketed as dietary supplements. Herein, the designer steroid methyl-1-testosterone (M1T) (17β-hydroxy-17α-methyl-5α-androst-1-en-3-one) was identified, and its biological activity, potential adverse effects, and metabolism were investigated. The affinity of M1T toward the androgen receptor (AR) was tested in vitro using a yeast AR transactivation assay. Its tissue-specific androgenic and anabolic potency and potential adverse effects were studied in a Hershberger assay (sc or oral), and tissue weights and selected molecular markers were investigated. Determination of M1T and its metabolites was performed by gas chromatography mass spectrometry. In the yeast AR transactivation assay, M1T was characterized as potent androgen. In rats, M1T dose-dependently stimulated prostate and levator ani muscle weight after sc administration. Oral administration had no effect but stimulated proliferation in the prostate and modulated IGF-I and AR expression in the gastrocnemius muscle in a dose-dependent manner. Analysis of tyrosine aminotransferase expression provided evidence for a strong activity of M1T in the liver (much higher after oral administration). In rat urine, 17α-methyl-5α-androstane-3α,17β-diol, M1T, and a hydroxylated metabolite were identified. In humans, M1T was confirmed in urine in addition to its main metabolites 17α-methyl-5α-androst-1-ene-3α,17β-diol and 17α-methyl-5α-androstane-3α,17β-diol. Additionally, the corresponding 17-epimers as well as 17β-hydroxymethyl-17α-methyl-18-nor-5α-androsta-1,13-dien-3-one and its 17-epimer were detected, and their elimination kinetics was monitored. It was demonstrated that M1T is a potent androgenic and anabolic steroid after oral and sc administration. Obviously, this substance shows no selective AR modulator characteristics and might exhibit liver toxicity, especially after oral administration.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                ibju
                International braz j urol
                Int. braz j urol.
                Sociedade Brasileira de Urologia (Rio de Janeiro )
                1677-6119
                September 2013
                : 39
                : 5
                : 675-682
                Affiliations
                [1 ] Universidade do Estado do Rio de Janeiro Brazil
                Article
                S1677-55382013000500675
                10.1590/S1677-5538.IBJU.2013.05.10
                24267110
                35219433-2ae1-4412-be67-351783ac82ac

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1677-5538&lng=en
                Categories
                UROLOGY & NEPHROLOGY

                Urology
                Prostate,Anabolic Agents,Nandrolone,Image Cytometry
                Urology
                Prostate, Anabolic Agents, Nandrolone, Image Cytometry

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