Many neuroendocrine and behavioral effects of ovarian steroid hormones are mediated by steroid receptors acting as gene regulators in neurons. However, besides being regulated by the hormones, hormone-receptor-containing neurons are part of neuronal networks, and therefore are influenced by afferent input from other neuroanatomical areas and environmental sources. In some cases, these afferent influences modulate the concentration of receptors, changing subsequent sensitivity to hormones; in other cases the afferent influences activate the receptors by a process known as ligand-independent activation, resulting in steroid receptor-dependent modification of neuronal responses. A model will be used in which genitosensory stimulation enhances the expression of reproductive behaviors by activation of neuronal progesterone receptors. Hypotheses concerning the neuroanatomical sites and cellular processes by which afferent input from social environmental sources influences the function of the progesterone receptor-containing neurons will be tested. Discrete neuroanatomical areas will be identified that are essential for transduction of this afferent information, resulting in progesterone receptor-dependent, ligand-independent, neuronal and behavioral changes. Then the dopaminergic cell groups involved will be determined. The hypothesis will be tested that genitosensory stimulation induces some neuronal and behavioral changes by the same progesterone-receptor-dependent, intracellular mechanism that D1 dopamine receptor stimulation does. The long-range goal of this research is to understand the processes by which the social environment, acting via neurotransmitters, influences neuronal, steroid hormone receptors to modulate the expression of behaviors and other neuroendocrine events. Because of the importance of steroid hormones and dopamine in the etiology and treatment of some affective disorders, the study of the influences of dopamine and environmental stimulation on steroid hormone receptors may be of great relevance to human health.
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