The potential roles of estrogens in regulating Leydig cell development andfunction: A review

It is generally agreed that estrogens, principally estradiol-17 beta, are s ynthesized by and act in the testis of mammals, including humans. The site of estradiol synthesis in the testis is generally believed to begin in the Sertoli fell and switch to the Leydig cell during neonatal development wher e a gonadotropin-regulated aromatase is present. Numerous studies suggest t hat the primary target cell of estradiol in the testis at all ages is the L eydig cell. In fact, the Leydig cell is known to possess an estrogen recept or that binds estradiol in the classic manner. The mechanism of estradiol a ction and the role of its receptor in the testis, however, remain unresolve d. In Leydig tells, estradiol appears to induce several alterations that ar e dependent in large part on the developmental stage of the Leydig cell. In the fetal and neonatal testes, estradiol appears to block the ontogenic de velopment of Leydig cells from precursor cells. There is also evidence that estradiol similarly blocks the regeneration of Leydig cells in the testis of mature, ethane dimethylsulfonate-treated animals. Evidence indicates tha t the precursor cell possesses high levels of estrogen receptors relative t o that of the Leydig cell. It is postulated that estradiol is a paracrine f actor involved in regulating the interstitial population of Leydig cells. E vidence also indicates that estradiol acts directly in the mature testis to block androgen production. It appears to do so by inhibiting the activitie s of several steroidogenic enzymes involved in testosterone synthesis. Alth ough the more conventional receptor-mediated mode of action is feasible, se veral studies have suggested that this action might entail direct competiti ve inhibition of key steroidogenic enzymes by estradiol. In summary, the ne t biologic effect of estradiol in the testis appears to be inhibition of an drogen production, either by limiting development and growth of the Leydig cell population or through direct action in the Leydig cell. (C) 1999 Elsev ier Science Inc. All rights reserved.