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 inhibit the LH surge, we investigated whether the progesterone receptor antagonist, RU486, could block the inhibitory effects of progesterone. Accordingly, intravaginal progesterone implants were inserted into OVX Ile-de-France ewes (n = 18), bearing 10 mm Silastic 17beta-oestradiol implants. Ten days later, the progesterone implants were removed, whereupon new implants were inserted immediately into 12 ewes: six of which were also injected with 100 mg RU486 dissolved in 10 mL vehicle (10% alcohol in peanut oil) and six received vehicle only. The remaining six ewes were injected with vehicle only. RU486 and vehicle injections were made again 12 and 24 h later. After the last injection, oestrogen concentrations were raised to peak follicular phase levels in all ewes by subcutaneous insertion of four 3-cm 17beta-oestradiol implants. Blood samples were collected every 2 h for 40 h starting 9 h after the insertion of the oestrogen implants. As expected, the six ewes treated only with oestradiol had a LH surge whereas no ewes given the implants in the presence of progesterone surged. RU486 completely blocked the inhibitory effect of progesterone. There were no differences in the time of LH surge 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 activation of the GABA(A) receptor. Rather, our study demonstrates that this effect is transduced by the classic nuclear progesterone receptor.