Effect of neonatal administration of estrogen, antiestrogen, and testosterone on the histological picture and estrogen receptor pattern of the adult rat prostate Mohamed D.M. El-Shafei a , Mohamed E.A. Mostafa b and Taymour Mostafa c Departments of a Histology, b Anatomy and c Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo, Egypt Correspondence to Taymour Mostafa, MD, Department of Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt Tel: +20 10 515 029 7; fax: +20 22 36 541 33; e-mail: taymour1155@link.net Received 26 September 2012 Accepted 25 December 2012 Human Andrology 2013, 3:1–5 Background Normal sexual development and functioning of the male reproductive organs are primarily controlled by androgens. However, estrogen also plays a role in the normal development, although this is not well defined. Aim The aim of this study was to assess the effect of neonatal administration of estrogen (E), antiestrogen (AE), and testosterone (T) on the histological picture and estrogen receptor (ER) pattern of the adult rat prostate. Materials and methods In all, 40 male albino rats at the age of 2 days were divided into four equal groups: untreated controls, rats that received E, those that received AE, and those that received T orally for 5 days starting from the second day. All rats were euthanized at the age of 6 weeks, after which specimens from the ventral lobe of the prostate were obtained. Main outcome measures Histopathological and immunohistochemical analysis of the investigated sections. Results In the E-treated rats, the diameter of the prostatic acini was reduced with increased fibromuscular stroma and epithelial hyperplasia. AE-treated or T-treated rats showed no histological changes compared with controls. The prostate of E-treated rats exhibited strong immunoreactivity against the ER compared with that of AE-treated or T-treated rats. The mean area percentage of ER immunoreactivity showed significant increase in E-treated rats compared with the controls, AE-treated rats, and T-treated rats. Conclusion The prostate, despite being an androgen-dependant gland, on exposure to E early in life could undergo structural disturbances that might lead to the development of prostatic disorders later. Keywords: antiestrogen, development, estrogen, prostate, testosterone Hum Androl 3:1–5 & 2013 Human Andrology 2090-6048 Introduction The complex control and integration of the reproductive system, relying on multilevel hormonal control and autonomic nervous input, makes altered function of one component have diverse secondary effects on other components when considering the mechanism of action or toxicity [1–4]. The normal development and function of male repro- ductive organs are primarily controlled by androgens. In addition, estrogen (E) was demonstrated to play a role evidenced by the presence of estrogen receptors (ER) in the male reproductive tract [5]. E in itself is an important morphogen and many of its proliferative epithelial effects are mediated by growth factors secreted from the stroma. E signaling was shown to be balanced between two opposing distinct receptors (ER-a and ER-b) and their splice variants [6]. The prospect that these two pathways can be selectively stimulated or inhibited with subtype- selective drugs still constitutes to be a promising therapeutic opportunity in clinical areas [7]. Different studies have pointed to the hazardous effect(s) of exogenous E on the reproductive organs of both developing and mature males [8]. Administration of E to developing fetuses or neonates has been demonstrated to produce pronounced short-term and long-term effects on the growth, histology, and functional activity of different reproductive organs [9]. As the male reproductive tract is more sensitive to the deleterious effects of E during early development, assessing these effects experimentally could reflect on the mechanisms occurring within humans. Nevertheless, androgens can be aromatized into E that binds to a specific, high-affinity ER protein in the Original article 1 2090-6048 & 2013 Human Andrology DOI: 10.1097/01.XHA.0000423420.15162.3d Copyright © Human Andrology. Unauthorized reproduction of this article is prohibited.