Introduction

Carcinoma of the prostate is the most frequently occurring malignancy and the second leading cause of cancer death in men in the US and many Western countries [1]. Notwithstanding the importance of this malignancy,little is understood about its causes. Sex steroids, particularly androgenic hormones, are suspected to play a major role in human prostate carcinogenesis. However, the precise mechanisms by which androgens affect this process and the possible involvement of estrogenic hormones are not clear. A causal relation between androgens and prostate cancer development is biologically very plausible because most human prostate cancers are androgen-sensitive and respond to hormonal therapy by remission which is later followed by relapse to a hormone-refractory state. The purpose of this overview is to summarize the literature about the role of sex steroids in prostate carcinogenesis. Although the objective of this overview is to explore the involvement of not only endogenous sex steroids but also a possible role of environmental hormonal factors, very little is know about exogenous chemicals with sex hormone activity in relation to prostate cancer.

The prostate is rarely a site of tumor development in carcinogenesis bioas-says in rodents [2,3], or in aging male laboratory rodents, with the exception of ventral prostatic neoplasms in some rat strains [4-9]. Prostate cancer is also very uncommon in male farm and companion animals, with the exception of the dog that is the only species besides man that develops this malignancy. As will be discussed in this review, sex steroid hormones can induce and substantially enhance prostate cancer development in rodents, and this phenomenon can serve as a model to study the involvement and mechanisms of sex steroids in prostate cancer etiology.

In this review, the epidemiological evidence for a role of sex steroids in prostate carcinogenesis is summarized first, followed by an overview of experi mental data and a discussion of the possible mechanisms whereby sex steroids, androgens as well as estrogens, may be involved in prostate cancer causation. Although there are several hypotheses about the role of sex steroids in prostate cancer etiology, the available data are often contradictory and incomplete, and an in-depth mechanistic understanding of how sex steroid hormones are involved in prostate carcinogenesis is poor at best.

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