Role of estrogen in regulation of cellular differentiation: a study using human placental and rat Leydig cells

Estrogen classically is recognized as a growth-promoting hormone. Recent evidence suggests that estrogens are also involved in a wide variety of cellular and physiological functions involving the central nervous system, immune system, cardiovascular system and bone homeostasis. Our studies in cytotrophoblasts and BeWo cells, demonstrated that 17beta-estradiol induces terminal differentiation of placental trophoblasts directly and this differentiation is coupled with an increased production of TGFbeta1, which, in turn, affects telomerase activity and telomerase associated components at the level of hTERT. Furthermore, using rats treated in vivo with either EDS or estradiol and in vitro Leydig cell cultures, we proposed that 17beta-estradiol mediated down-regulation of collagen IV alpha4 expression could be one of the possible mechanisms for the inhibition of progenitor Leydig cell proliferation. In this review, we summarize the results from both the model systems, the human placental cytotrophoblast and rat Leydig cells to conclude that 17beta-estradiol has a unique stage-specific role in differentiation.