Further investigation of the antiovulatory effects of the antiprogestational steroid RMI 12,936 in the rat.

Inhibition of ovulation by RMI 12,936 was associated with suppression of the pro-oestrous peak of hypothalamic dopamine. The antiovulatory effect was not reversed by administration of oestrogen, was partly reversed by progesterone and was fully reversed by oestrogen and progesterone. Hypophysial sensitivity to LH-RH, known to be reduced by RMI 12,936, remained low when ovulation was restored by steroid treatment. Administration of oestrogen did not restore the pro-oestrous peak of hypothalamic dopamine and ovulation was not induced following administration of L-DOPA in RMI 12,936-treated animals. It was concluded that RMI 12,936 is antioestrogenic as well as antiprogestational, that oestrogen is necessary for induction of full hypothalamic-hypophysial responsiveness to progesterone and that a hypothalamic dopaminergic pathway may have a non-essential role in the control of ovulation possibly associated with increasing hypophysial sensitivity to LH-RH.