The progesterone blockade of the luteinizing hormone surge is overcome by RU486

Progesterone can prevent the oestrogen-induced and spontaneous preovulatory luteinizing hormone (LH) surges but the mechanisms underlying this effect remain poorly understood. Using a follicular phase ovariectomised (OVX) ewe model and by elevating progesterone in the presence of oestrogen to inhibi t the LH surge, we investigated whether the progesterone receptor antagonis t, RU486, could block the inhibitory effects of progesterone, Accordingly, intravaginal progesterone implants were inserted into OVX Ile-de-France ewe s (n =18), bearing 10 mm Silastic 17 beta-oestradiol implants. Ten days lat er, the progesterone implants were removed, whereupon new implants were ins erted immediately into 12 ewes: six of which were also injected with 100 mg RU486 dissolved in 10 mt vehicle (10% alcohol in peanut oil) and six recei ved vehicle only. The remaining six ewes were injected with vehicle only, R U486 and vehicle injections were made again 12 and 24 h later. After the la st injection, oestrogen concentrations were raised to peak follicular phase levels in all ewes by subcutaneous insertion of four 3-cm 17 beta-oestradi ol implants, Blood samples were collected every 2 h for 40 h starting 9 h a fter the insertion of the oestrogen implants. As expected, the six ewes tre ated only with oestradiol had a LH surge whereas no ewes given the implants in the presence of progesterone surged, RU486 completely blocked the inhib itory effect of progesterone, There were no differences in the time of LH s urge onset, duration over which LH levels remained above their half-maximal concentration or magnitude of the LH surge between the two groups showing surges. Our study suggests strongly that the progesterone-mediated blockade of the ovine oestrogen-induced LH surge is not through allopregnanolone ac tivation of the GABA(A) receptor, Rather, our study demonstrates that this effect is transduced by the classic nuclear progesterone receptor.