Sources of oestrogen in the testis and reproductive tract of the male

Abstract

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the irreversible transformation of androgens into oestrogens and is present in the endoplasmic reticulum of various tissues throughout at least the phylum of vertebrates. The CYP 19 gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons. The P450arom has been immunolocalized in germ cells of the mouse, brown bear and rooster. According to age, aromatase activity has been measured in immature and mature rat Leydig cells as well as in Sertoli cells, whereas in the pig, ram and human aromatase is mainly present in Leydig cells. In the adult rat testis, four complementary approaches (RTPCR, in situ hybridization, immunocytochemistry and the tritiated water assay) demonstrate that not only somatic cells but also mature germ cells represent a source of oestrogen synthesis. Taking into account the widespread distribution of oestrogen receptors (ER alpha & ER beta) in testicular cells and the genital tract of the male on the one hand, and the cross-talk between sex steroids and growth factors, and between membrane receptors and nuclear receptors for steroids on the other hand, it is anticipated that understanding of the pathophysiological roles of these 'female' hormones in the male will advance understanding of the hormonal regulation of male reproductive function. One of the future goals is to define oestrogen-targeted genes in the male gonad and indeed, a lot of work is now focused on this specific area in order to clarify the role of oestrogens in the reproductive tract of the male as well as to elucidate the regulation of aromatase gene expression.

Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors

“…However, in the past decade there has been a growing body of evidence that germ cells could also synthesise oestrogens. In fact, the presence of aromatase has been demonstrated in germ cells of a great number of species , Janulis et al 1998, for review see Carreau et al 1999).…”

Expression of estrogen receptor-alpha and -beta mRNAs in the male reproductive system of the rat as revealed by in situ hybridization

“…Produced mainly in the ovary and adrenal gland in the female, estrogen exerts a strong influence over reproductive events (Freeman 1988). Although the presence of estrogen in the male gonad has been well documented for more than 50 years (see review by Carreau et al 1999), it is only recently that studies on the exact role of estrogen in male reproduction and fertility have been undertaken (Meistrich et al 1975, Couse & Korach 1999, Hess 2000, Lee et al 2000. Aromatase, a microsomal enzymatic complex which irreversibly converts androgens into estrogen, has been demonstrated in testicular cells including Sertoli and Leydig cells and, more recently, in germ cells (Janulis et al 1998, Carreau et al 1999.…”

“…Although the presence of estrogen in the male gonad has been well documented for more than 50 years (see review by Carreau et al 1999), it is only recently that studies on the exact role of estrogen in male reproduction and fertility have been undertaken (Meistrich et al 1975, Couse & Korach 1999, Hess 2000, Lee et al 2000. Aromatase, a microsomal enzymatic complex which irreversibly converts androgens into estrogen, has been demonstrated in testicular cells including Sertoli and Leydig cells and, more recently, in germ cells (Janulis et al 1998, Carreau et al 1999. Even though the overall production of estrogen by the testis, which is the major source of estrogen in the male, is much less than that produced by the ovaries, the concentration of estrogen in the rete testis and caput epididymis fluids has been reported to be higher than serum estradiol in the female (Hess et al 1997b).…”

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

“…Two isoforms of estrogen receptors (ERs)-ER␣ and ER␤-have also been localized in several male reproductive tissues (Iguchi et al, 1991;Kuiper et al, 1997;Pelletier, 2000;Atanassova et al, 2001;Zhou et al, 2002). Although the roles of estrogens in male reproductive organs are still poorly understood, estrogens are widely believed to participate in normal and abnormal processes of male physiology through ERs (Iguchi, 1992;Carreau et al, 1999;Hess et al, 2001). Recent studies using ER␣-knockout mice have demonstrated the presence of ER␣ in the ductuli efferentes to be essential for luminal fluid absorption from the testis (Hess et al, 1997;Lee et al, 2000).…”