Progesterone and subsequent polar metabolites are essential for completion of the first meiotic division in amphibian oocytes

We find that completion of the first meiotic division in Rana pipiens oocytes requires the sequential action of at least two steroids: progesterone and one or more subsequent polar metabolites of progesterone. Progesterone binding in vitro to oocyte surface receptors increases during the first 4–5 h of exposure, followed by internalization of plasma membrane together with membrane-bound progesterone over the next hour. The internalized progesterone is metabolized to highly polar polyhydroxylated steroid(s) prior to nuclear membrane disappearance at 8–9 h. Polar steroids alone cannot induce meiosis, but do so in oocytes pretreated with progesterone for 1 h. Similarly, the non-metabolizable progestin R5020 cannot induce meiosis but does if oocytes are subsequently exposed to polar steroids. An inhibitor of steroid α-reductase (4-MA) prevents both progesterone metabolism and progesterone-induced meiosis. However, meiosis does occur if 4-MA is followed by a polar steroid. Thus, progesterone binding at the oocyte surface initiates a process which requires polar progesterone metabolites for completion of the first meiotic division.