Estrogens in testis biology

Abstract

Levels of estrogen within the male reproductive tract are higher than in the general circulation and the aromatase enzyme is expressed in the adult testis. Estrogens such as estradiol (E2) modify cell function by binding to high-affinity estrogen receptors (ER). Two subtypes (ERalpha and ERbeta) have been identified. Studies in animals have shown that over- or underexposure to estrogens can have an impact on testis function. For example, mice with targeted disruption of the aromatase cyp19 gene become infertile because round spermatids fail to differentiate normally. In rodents, ERalpha is expressed in Leydig cells; ERalpha mRNA and protein are not detectable in testes from humans or primates. High levels of expression of ERalpha occur in the efferent ductules in rodents, primates, and the human. ERbeta protein has been immunolocalized to all somatic cells and to some germ cells in these same species. Messenger RNAs for splice variant isoforms of human ERbeta are expressed in human testes. Homologues of the ERbeta2 variant have been cloned from primates; this isoform does not exist in rodents and does not bind E2. Full-length ERbeta protein (ERbeta1) and ERbeta2 have differential patterns of expression in human testes. In conclusion, although estrogens are synthesized in the testis and it has been suggested that E2 may function as a germ cell survival factor, the mechanisms by which estrogens influence male fertility remain uncertain and rodents may be poor models in which to examine this.