![]() ![]() Furthermore, the presence of estrogen-response-elements (EREs) on the promoter region of the β-subunit of the LH gene has been reported, implying that estrogen regulation of LH secretion occurs directly at the level of the LHβ gene. For example, E2 treatment of a mouse gonadotroph cell line (LβT2) increased LH secretion and, following co-incubation with GnRH, increased LHβ mRNA levels. There is conclusive evidence showing that ERα and ERβ are present in several hypothalamic nuclei and in pituitary gonadotropes, indicating that estrogen regulates the hypothalamus-pituitary axis. In contrast, ERs have a more diversified pattern of expression. Indeed, FSH receptors are expressed only in Sertoli cells, and Leydig cells are the only binding sites for LH in the testis. ![]() FSH and LH are the primary tropic hormones that regulate testicular function. Gonadal steroids act on the hypothalamus to affect GnRH pulses, and at the pituitary level to regulate gonadotropin (FSH and LH) secretion. Īlthough the present review is focused on direct estrogen action in the testis, estrogen regulation may occur indirectly by changes caused in the hypothalamus and pituitary. In consonance with localization studies, mice which have targeted deletion of the aromatase gene, ERα and/or ERβ showed altered testicular morphology and derangements of spermatogenesis, and exposures of laboratory species and wildlife to estrogenic chemicals were found to cause abnormalities of the reproductive tract. Evidence from several studies indicates that aromatase, ERα and ERβ are encoded by separate genes but are co-expressed with androgen receptors in the male reproductive tract. The serum levels of E2 measure about 40 pg/mL in male rats, and ranges between 20 and 40 pg/mL in men. The aromatization of C19 androgens, i.e., testosterone and androstenedione, is a key step in estrogen (E2) biosynthesis and is catalyzed by the aromatase enzyme, which is a product of the CYP19 gene. Growing public concerns that exposures to environmental chemicals with estrogenic activity may impact human reproductive health have focused attention on the role of estrogen in male reproductive health. However, recent observations challenge the dogma that the male phenotype is maintained solely by testosterone binding to its protein target, i.e., the androgen receptor. Leydig cells are the predominant source of the male sex steroid hormone testosterone. The interstitium consists of loose connective tissue, blood and lymphatic vessels, and various cell types, including Leydig cells, fibroblasts, macrophages and leukocytes. Seminiferous tubules are lined by layers of germ cells in various stages of development (spermatogonia, spermatocytes, spermatids, spermatozoa) and supporting Sertoli cells. The testis consists of two compartments: seminiferous tubules and intertubular tissue, which forms the interstitium. Use of tissue-specific knockout animals and administration of antiestrogens and/or aromatase inhibitors in vivo may generate additional data to advance our understanding of estrogen and estrogen receptor biology in the developing and mature testis. However, studies of estrogen action are confounded by a number of factors, including the inability to dissociate estrogen-induced activity in the hypothalamus and pituitary from action occurring directly in the testis and expression of more than one ER subtype in estrogen-sensitive tissues. ![]() ![]() Moreover, several chemicals that are present in the environment, designated xenoestrogens because they have the ability to bind and activate ERs, are known to affect testicular gene expression. Estrogen is thought to have a regulatory role in the testis because estrogen biosynthesis occurs in testicular cells and the absence of ERs caused adverse effects on spermatogenesis and steroidogenesis. These studies fall into three categories: i) localization of aromatase and the target protein for estrogen (ER-alpha and ER-beta) in tissues of the reproductive tract ii) analysis of testicular phenotypes in transgenic mice deficient in aromatase, ER-alpha and/or ER-beta gene and, iii) investigation of the effects of environmental chemicals on male reproduction. Evidence supporting a role for estrogen in male reproductive tract development and function has been collected from rodents and humans. ![]()
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