Tibolone induces lordosis behavior, but not concurrent or sequential inhibition, in Sprague Dawley rats

Activation of Progesterone Receptor (PR) facilitates lordosis 40 hr after estradiol treatment, but induces concurrent inhibition (CI) when given with estradiol, or sequential inhibition (SI) when given subsequent to the faciliatory time interval. Tibolone (TBL) is a broad spectrum gonadal steroid agonist that facilitates lordosis when given after estradiol and in place of progesterone (P). The present experiment examined whether it can also induce CI or SI of lordosis behavior in rats as a means of determining its dominant receptor mechanism of action. Subcutaneous (SC) injections of estradiol benzoate (EB), TBL, or P were varied in time to examine whether P induced CI in females pre-treated with TBL or EB, or whether P or TBL induced CI when injected prior to EB (Experiment 1); whether P or TBL induced SI after EB treatment (Experiment 2); and whether P induced SI after TBL treatment (Experiment 3). In Experiment 1, P injected 1 h before EB induced CI after a second P administration 40 h later. However, the same treatment of P to females primed with TBL did not induce CI. In Experiment 2, injections of P or TBL 40 h after EB or TBL induced lordosis within 4 h (facilitation test); however, a second injection of P, 24 h later, induced significant lordosis in rat pretreated with TBL, but not in rats pretreated with P (inhibition test). In Experiment 3, P injected 40 hs after different doses of TBL induced intense lordosis behavior (facilitation test); however, a second dose of P injected 64 h later induced SI, but not in females primed with the highest dose of TBL (inhibition test). Unlike P, TBL did not induce CI or SI. This suggests that TBL likely induces its facilitation of lordosis by an action that is independent of PR.