REVERSAL OF PROGESTERONE-INDUCED SEQUENTIAL INHIBITION BY PROGESTERONE METABOLITES

Previous reports have shown that intrabrain administration of progeste rone (P) ring A-reduced metabolites into the medial preoptic ar ea (MP OA) 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) Spragu e Dawley rats implanted with guide cannulae directed towards the VMH o r the MPOA were submitted to a systemic hormonal treatment to provoke P-induced sequential inhibition (estradiol benzoate (EB) at time 0 + P at 44 h + P at 68 h). The second dose of P was administered simultane ously with the ic implantation of one of the following P metabolites: 3 beta-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P), 3 alpha-hydro xy-5 beta-pregnan-20-one (5 beta,3 alpha P) or 3 beta-hydroxy-5 beta p regnan-20-one (5 alpha,3 beta P) into the MPOA or VMH. Lordosis behavi or was evaluated by the lordosis quotient (LQ = number of lordosis/10 male mount x 100) and by the percentage of responding subjects. Result s show that 5 beta,3 beta P implanted into the VMH or MPOA counteracte d the sequential inhibitory effect induced by systemic administration of P.5 alpha,3 beta P was also able to counteract sequential inhibitio n, but with less potency and only in the VMFI. Results show that P-ind uced sequential inhibition can be counteracted by intrabrain administr ation of ring-A reduced progestins in both the VMH and MPOA. Data are discussed in terms of a putative physiological role of naturally occur ring P metabolites in P-mediated female sexual behavior expression.