This notion is further supported from the observation that enhanced NMDA receptor activation alone is sufficient to mimic estradiol and induce a sex difference in the neuronal morphology of the neonatal hypothalamus (Schwarz et al, 2008) and defeminize behavior in adulthood. In the adult, glutamate receptor activation OT-R antagonist 2 in the hypothalamus OT-R antagonist 2 inhibits the expression of lordosis (Georgescu and Pfaus, 2006a; Georgescu and Pfaus, 2006b; McCarthy et al, 1991). of estradiol-induced defeminization of behavior. We statement here that antagonizing glutamate receptors during the essential period of sexual differentiation blocks estradiol-induced defeminization but not masculinization of behavior in adulthood. However, enhancing NMDA receptor activation OT-R antagonist 2 during the same essential period mimics estradiol to permanently induce both defeminization and masculinization of sexual behavior. Intro Sex variations in the brain underlie sex variations in behavior, and this association is best characterized for rat sexual behavior. Sex variations in OT-R antagonist 2 mind and behavior are identified during a sensitive period of development, with the hormone estradiol becoming critically important. In the male rat, the embryonic and neonatal testes produce testosterone that is locally aromatized to estradiol in select nuclei of the brain. In rats and mice, the essential period for sexual differentiation begins before birth and ends approximately 10 days after birth. Within that time, treatment of females with exogenous estradiol will mimic the effect of endogenous estradiol in the male, to permanently switch the brain and behavior in adulthood (Schwarz and McCarthy, 2008). The normal development of the male mind requires completion of two unique processes: masculinization and defeminization (Baum, 1979). Masculinization is OT-R antagonist 2 the organization of a neural substrate permissive to the manifestation of male sexual behavior. Defeminization is the loss of capacity to respond to the activational effects of estradiol and progesterone to induce female sex behavior. Both processes oppose the process of feminization that induces the capacity to respond to estradiol and progesterone in adulthood with lordosis, or female sexual receptivity. Feminization happens in the absence of essential levels of neuronal estradiol during the neonatal essential period (Baum, 1979; Nordeen and Yahr, 1983). Improvements are becoming made in understanding the mechanisms by which steroids induce masculinization of the brain and behavior, but little is definitely know concerning the concurrent process of defeminization. The preoptic area (POA) is definitely a mind region necessary for male sex behavior and the mediobasal hypothalamus (MBH) is definitely a mind region necessary for female sex behavior. Both areas are key focuses on of estradiol in development and in adulthood. In the neonatal POA and the MBH, males have two-three instances more dendritic spines and spine synapses than females (Amateau and McCarthy, 2002; Matsumoto and Arai, 1980; Matsumoto and Arai, 1986; Raisman and Field, 1973; Raisman, 1974; Todd et al, 2005; Todd et al, 2007), which are induced by estradiol during the essential period (Amateau and McCarthy, 2002; Todd et al, 2005; Todd et al, 2007). Estradiol induces dendritic spine formation in the POA by increasing the production of prostaglandin E2 (PGE2) via up-regulation of its synthesizing enzyme cyclooxygenase-2 (COX-2) (Amateau and McCarthy, 2002). Treatment of females with PGE2 mimics the effect of estradiol to increase dendritic spines on neurons in the POA (Amateau and McCarthy, 2002; Amateau and McCarthy, 2004), but does not increase the quantity Mouse monoclonal to MBP Tag of dendritic spines on neurons in the neighboring MBH (Todd et al, 2005). Instead, estradiol raises dendritic spines in the developing MBH by enhancing glutamate launch from presynaptic terminals to increase the activation of AMPA and NMDA glutamate receptors on postsynaptic hypothalamic neurons (Todd et al, 200; Schwarz et al, 2008). Conversely, while activation of NMDA receptors is necessary and adequate for estradiol to increase dendritic spines in the MBH during the essential period of development (Schwarz et al, 2008), activation of NMDA receptors is not necessary for estradiol or PGE2 to increase dendritic spines in the developing POA (Amateau and McCarthy, 2002). We have previously identified that treatment of newborn female rat pups with PGE2 selectively induces total masculinization of sex behavior in adulthood. Conversely, obstructing estradiol-induced production of PGE2 using a COX-2 inhibitor, prevents masculinization of sex behavior (Amateau and McCarthy, 2002; Amateau and McCarthy, 2004). However, these manipulations have no effect on the manifestation of female sex behavior, leaving the process of estradiol-induced defeminization intact (Todd et al, 2005). Taken together, these results lead to two conclusions; 1) estradiol-induced sex variations in neuronal morphology of the POA are not the site of estradiol-induced defeminization of behavior, 2) estradiol-induced sex variations in neuronal morphology of the MBH are not the underlying site.
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