| Abstrakt: |
The essential role of steroids in the mediation of gonadotropic stimulation of oocyte maturation in amphibians and fish is well established. Such role of steroids in the regulation of meiosis in mammals has not been confirmed convincingly until recently. Recently a series of publications from the laboratory of Hammes presented evidence that steroids mediate LH action on resumption of meiosis in the mouse and the rat (2004–06). In these studies it was claimed that progesterone, estrogen or testosterone can stimulate resumption of meiosis and that specific antagonists of each of these steroid receptors can block this action of LH. Here we examine the suggested role of progesterone and estrogen in the mediation of LH-stimulated resumption of meiosis in the rat and the mouse. These steroids were examined due to their previously shown transient rise in the preovulatory follicles in response to LH/hCG. In vitro cultures of rat and mouse preovulatory follicle-enclosed oocytes (FEOs) and cumulus-enclosed oocytes (CEOs) were used. FEOs, which mature only in response to gonadotropins or other stimuli, were used to test the ability of steroids to trigger meiosis or to test whether steroid antagonists block LH-induced resumption of meiosis. The spontaneous resumption of meiosis in CEOs was blocked by the purine hypoxanthine (Hx; 4mM), a mild inhibitor of phosphodiesterases. This model was used to test the ability of steroids to overcome the inhibition of meiosis by Hx. The progesterone antagonists mifepristone (RU 486; 25–50 μM) and Org 31710 (1–10 μM), as well as the estrogen antagonist faslodex (25–50 μM), did not prevent LH-triggered maturation of rat FEOs. In accordance, the progesterone agonist, promegestone (R5020; 250–1000nM) and estradiol (250–1000 nM) did not stimulate the resumption of meiosis in rat and mouse FEOs, and both (100–250 nM) did not overcome the Hx inhibition of spontaneous meiosis in rat and mouse CEOs. By contrast, progesterone and promegestone induced the maturation of Xenopus oocytes. Contrary to recent claims, we could not provide evidence that progesterone or estrogen mediate LH stimulation of meiosis in rodents. Thus, in stark contrast to lower vertebrates, these steroids do not seem to serve as an obligatory signal by which the somatic cells of the follicle transfer the gonadotropic stimulation of meiosis to the oocyte. We suggest that this may be associated with the evolution of hierarchical follicle growth in mammals and ovulation of one or a few oocytes each cycle and the resulting high steroid levels in the ovary. Such local abundance of steroids in the ovary presumably precludes their use in mammals as a signal for the resumption of meiosis. Nevertheless, the finding that these steroids do not serve as mediators in the stimulation of meiotic resumption does not imply that they are not involved in oocyte development and ovulation. It has been shown previously that estrogen is involved in the acquisition of meiotic and developmental competence and progesterone is necessary for cumulus expansion and follicle rupture. (poster) |
