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Animal models, in particular rodents, have provided insight into general principles and the cellular and molecular mechanisms of brain differentiation. Cellular endpoints influenced by steroids in the developing brain include neurogenesis, migration, apoptosis, dendritic growth, and synaptic patterning. Important roles for prostaglandins, endocanabinoids, and epigenetics are among the many cellular mediators of hormonal organization. Transference of general principles of brain sexual differentiation to humans relies on observations of individuals with genetic anomalies that either increase or decrease hormone exposure and sensitivity. The physiology and behavior of individuals with XXY (Klinefelter syndrome) has not been considered in the context of sexual differentiation of the brain, most likely due to the delay in diagnoses and highly variable presentation. The behavioral phenotype and impairments in the domains of speech and language that are characteristic of individuals with XXY is consistent with the reduced androgen production associated with the syndrome. Hormone replacement appears effective in restoring some deficits and impact may be further improved by increased understanding of the hormonally mediated sexual differentiation of the brain. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.31351","type":"journal-article","created":{"date-parts":[[2013,1,19]],"date-time":"2013-01-19T04:34:24Z","timestamp":1358570064000},"page":"3-15","source":"Crossref","is-referenced-by-count":10,"title":["Sexual differentiation of the brain in man and animals: Of relevance to Klinefelter syndrome?"],"prefix":"10.1002","volume":"163","author":[{"given":"Margaret M.","family":"McCarthy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000324402"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2009.01871.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1286.024"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.05.028"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01221-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000102103"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32833e7866"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/2042-6410-1-8"},{"key":"e_1_2_7_10_1","article-title":"Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval","author":"Bowers JM","year":"2012","journal-title":"J Neurosci"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-4-12-1759"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80099-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.03.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387687-4.00002-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2004.11.004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2919-05.2005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7538"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(00)00301-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.01.003"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.9.3.382"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-008-0003-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08032.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1350"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01541353"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0018-506X(89)90040-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222941"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.07.046"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.03.002"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn834"},{"key":"e_1_2_7_30_1","first-page":"1","article-title":"Molecular basis of androgen insensitivity","volume":"46","author":"French FS","year":"1990","journal-title":"Recent Prog Horm Res"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.05.013"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-04-01286.1990"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2012.11.006"},{"key":"e_1_2_7_34_1","article-title":"Klinefelter syndrome\u2014A clinical update","author":"Groth KA","year":"2012","journal-title":"J Endocrinol Metab"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2007.12.007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.220"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012532104-4\/50072-X"},{"key":"e_1_2_7_38_1","volume-title":"Brain gender","author":"Hines M","year":"2004"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2630225100"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.035"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/hbeh.2001.1670"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10508-010-9618-z"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2011.560280"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001471"},{"key":"e_1_2_7_45_1","unstructured":"KonkleATM McCarthyMM.2007. 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