An understanding of the cellular processes by which steroid receptors are activated has become increasingly relevant due to rising clinical importance. Steroid receptors located within the central nervous system are involved in altering both the behavior and physiology of an animal. One mechanism by which steroid hormone receptors may be activated is by a cognate ligand binding to the receptor. Recent studies have shown that steroid receptors also may be activated in vitro by modulators of protein phosphorylation in the absence of ligand. This is referred to as ligand-independent activation. More important, recent studies have found that ligand-independent activation of the progestin receptor may occur within the central nervous system using pharmacological manipulations. Indeed, ligand-independent activation of the progestin receptor, via pharmacological manipulations, facilitates reproductive behavior in estradiol-primed female rats. We have evidence that the progestin receptor may be activated in a ligand-independent manner under physiological and behaviorally relevant conditions in female rats. In the present series of experiments, we will attempt to further clarify ligand-independent activation of progestin receptors using a reproductively relevant stimulus. In addition, these experiments are designed to provide training in intracerebroventricular administration of antisense oligonucleotides and in situ hybridization.
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