Reversal of progesterone-induced sequential inhibition by progesterone metabolites

Previous reports have shown that intrabrain administration of progesterone (P) ring A-reduced metabolites into the medial preoptic area (MPOA) and ventromedial hypothalamus (VMH) induces facilitation of female sexual behavior in ovariectomized (ovx) rats pretreated with estrogen. Present studies were designed to explore the possibility that ring-A reduced progesterone metabolites might play a role in controlling the duration of estrous behavior. To this aim ovariectomized (ovx) Sprague Dawley rats implanted with guide cannulae directed towards the VMH or the MPOA were submitted to a systemic hormonal treatment to provoke P-induced sequential inhibition (estradiol benzoate (EB) at time O + P at 44 h + P at 68 h). The second dose of P was administered simultaneously with the i.c. implantation of one of the following P metabolites: 3 beta-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P), 3 alpha-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P) or 3 beta-hydroxy-5 beta- pregnan-20-one (5 alpha,3 beta P) into the MPOA or VMH. Lordosis behavior was evaluated by the lordosis quotient (LQ = number of lordosis/10 male mount x 100) and by the percentage of responding subjects. Results show that 5 beta,3 beta P implanted into the VMH or MPOA counteracted the sequential inhibitory effect induced by systemic administration of P.5 alpha,3 beta P was also able to counteract sequential inhibition, but with less potency and only in the VMFI. Results showed that P-induced sequential inhibition can be counteracted by intrabrain administration of ring-A reduced progestins in both the VMH and MPOA. Data are discussed in terms of a putative physiological role of naturally occurring P metabolites in P-mediated female sexual behavior expression.