Estrogen regulation of testicular function

Abstract

Evidence supporting a role for estrogen in male reproductive tract development and function has been collected from rodents and humans. These studies fall into three categories: i) localization of aromatase and the target protein for estrogen (estrogen receptors, ER-alpha and ER-beta); ii) analysis of transgenic mice deficient in the aromatase gene, ER-alpha and/or ER-beta; and, iii) investigation of the effects of environmental chemicals with estrogenic activity on male reproduction. Estrogen plays a role in the regulation of the testis testicular because estrogen biosynthesis is known to occur in diverse cell types within the testis, and absence of ERs caused adverse effects on spermatogenesis and steroidogenesis. Similarly, several chemicals present in the environment, designated xenoestrogens, have the ability to bind ERs and thereby affect testicular gene expression. However, the mechanisms associated with estrogen regulation of the testis under physiological conditions are only beginning to be clarified. This is due in part to the inability to dissociate estrogen-induced activity in the hypothalamus-pituitary axis from action occurring directly in the testis. Also, there are shortcomings in techniques used to measure the levels of aromatase and ER gene expression in various tissues. For example, the absence of estrogen-priming of extragonadal tissues that regulate reproductive activity during development (e.g., hypothalamus) in transgenic mice lacking endogenous estrogen production or ER protein is a confounding factor in the interpretation of data collected from these studies. Moreover, binding assays and early localization studies did not specify which ER subtype (ER-alpha or ER-beta) was present in specific tissues. New experimental approaches are needed to address these issues. For example, the development of techniques that do not perturb the hormonal milieu of gonadal tissues under study, e.g., use of tissue-specific knockout animals, and the selective administration of antiestrogens and/or aromatase inhibitors in vivo (e.g., intratesticular injections), may generate additional data to advance our understanding of the regulatory role of estrogen in the developing and mature testis. © 2005 Akingbemi; licensee BioMed Central Ltd.