Traditionally, steroid receptors were believed to be activated only by ligand binding; however, recent studies indicate that steroid receptors can also be activated by mechanisms that do not require ligand, referred to as ligand-independent activation. Specifically, progestin receptors can be activated in vitro and in vivo after treatment with neurotransmitters, such as dopamine, in the absence of progesterone. Furthermore, mating-related stimuli can also lead to ligand-independent activation of progestin receptors in female rat brain. This finding indicates that environmental stimuli can influence steroid receptor-dependent processes in the absence of circulating hormone. This review focuses on studies indicating that progestin receptors can be activated in the absence of progesterone to influence neuronal response and sexual behaviour in rodents.