Visualizing Sexual Dimorphism in the Brain

Sexually dimorphic behaviors are likely to involve neural pathways that express the androgen receptor (AR). We have genetically modified the AR locus to visualize dimorphisms in neuronal populations that express AR. Analysis of AR-positive neurons reveals both known dimorphisms in the preoptic area of the hypothalamus and the bed nucleus of the stria terminalis as well as novel dimorphic islands in the basal forebrain with a clarity unencumbered by the vast population of AR-negative neurons. This genetic approach allows the visualization of dimorphic subpopulations of AR-positive neurons along with their projections and may ultimately permit an association between neural circuits and specific dimorphic behaviors.

[1]  L. Swanson,et al.  Distribution of androgen and estrogen receptor mRNA‐containing cells in the rat brain: An in situ hybridization study , 1990, The Journal of comparative neurology.

[2]  S. Horvath,et al.  Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. , 2003, Brain research. Molecular brain research.

[3]  J. Pfaus,et al.  Implications of Immediate-Early Gene Induction in the Brain Following Sexual Stimulation of Female and Male Rodents , 1997, Brain Research Bulletin.

[4]  S. Davis,et al.  Another role highlighted for estrogens in the male: sexual behavior. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. Zumpe,et al.  Androgen receptor and mating-induced Fos immunoreactivity are co-localized in limbic and midbrain neurons that project to the male rat medial preoptic area , 1998, Brain Research.

[6]  T. Insel,et al.  Sexual and social experience is associated with different patterns of behavior and neural activation in male prairie voles , 1997, Brain Research.

[7]  A. Arnold,et al.  Sexual dimorphism in vocal control areas of the songbird brain. , 1976, Science.

[8]  S. M. Breedlove,et al.  Sexual Differentiation of the Vertebrate Brain: Principles and Mechanisms , 1998, Frontiers in Neuroendocrinology.

[9]  S. Maxson,et al.  Transcription of the Y chromosomal gene, Sry, in adult mouse brain. , 1995, Brain research. Molecular brain research.

[10]  N. Harada,et al.  Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. , 1998, Biochemical and biophysical research communications.

[11]  L. Geller,et al.  TfM mutation and masculinization versus feminization of the mouse central nervous system. , 1974, Cell.

[12]  S. Segovia,et al.  Sexual dimorphism in the vomeronasal pathway and sex differences in reproductive behaviors , 1993, Brain Research Reviews.

[13]  T. Saibara,et al.  A loss of aggressive behaviour and its reinstatement by oestrogen in mice lacking the aromatase gene (Cyp19). , 2001, The Journal of endocrinology.

[14]  A. Arnold,et al.  Hormone accumulation in a sexually dimorphic motor nucleus of the rat spinal cord. , 1980, Science.

[15]  J. Stringer,et al.  Human placental alkaline phosphatase as a histochemical marker of gene expression in transgenic mice , 1996, Transgenic Research.

[16]  M. Joppa,et al.  c-Fos expression in female hamster brain following sexual and aggressive behaviors , 1995, Neuroscience.

[17]  D. A. Edwards Early androgen stimulation and aggressive behavior in male and female mice , 1969 .

[18]  D. Pfaff,et al.  Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO). , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  T. Curran,et al.  Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. , 1991, Annual review of neuroscience.

[20]  R. Gorski,et al.  Two sexually dimorphic cell groups in the human brain , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  R. Simerly,et al.  Development of a Sexually Dimorphic Projection from the Bed Nuclei of the Stria Terminalis to the Anteroventral Periventricular Nucleus in the Rat , 1998, The Journal of Neuroscience.

[22]  A. Arnold,et al.  Sex differences in sex chromosome gene expression in mouse brain. , 2002, Human molecular genetics.

[23]  C. Cepko,et al.  A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Benjamin D. Sachs,et al.  Copulatory behavior in male rats with lesions in the bed nucleus of the stria terminalis , 1976, Physiology & Behavior.

[25]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[26]  F. Davis,et al.  Sexually dimorphic regions in the medial preoptic area and the bed nucleus of the stria terminalis of the guinea pig brain: a description and an investigation of their relationship to gonadal steroids in adulthood , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  R. Michael,et al.  Fos Induced by Mating or Noncontact Sociosexual Interaction Is Colocalized with Androgen Receptors in Neurons within the Forebrain, Midbrain, and Lumbosacral Spinal Cord of Male Rats , 1998, Hormones and Behavior.

[28]  Robin Lovell-Badge,et al.  A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits , 2002, The Journal of Neuroscience.

[29]  S. S. Winans,et al.  The differential projections of the olfactory bulb and accessory olfactory bulb in mammals , 1975, The Journal of comparative neurology.

[30]  William Rowan,et al.  The Study of Instinct , 1953 .

[31]  Peter Goodfellow,et al.  "Male Development of Chromosomally Female Mice Transgenic for Sry gene" (1991), by Peter Koopman, et al. , 2014 .

[32]  Y. C. Liu,et al.  Lesions in Medial Preoptic Area and Bed Nucleus of Stria Terminalis: Differential Effects on Copulatory Behavior and Noncontact Erection in Male Rats , 1997, The Journal of Neuroscience.

[33]  Hong-wei Dong,et al.  Topography of projections from amygdala to bed nuclei of the stria terminalis , 2001, Brain Research Reviews.

[34]  C. D. Jacobson,et al.  Evidence for the existence of a sexually dimorphic nucleus in the preoptic area of the rat , 1980, The Journal of comparative neurology.

[35]  E. Kandel The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[36]  E. K. Shriver,et al.  Sexual Differentiation , 1992, Handbooks of Behavioral Neurobiology.

[37]  Frederick Naftolin,et al.  Estrogen formation in the mammalian brain: Possible role of aromatase in sexual differentiation of the hippocampus and neocortex , 1987, Steroids.

[38]  D. Kelley,et al.  Neuroeffectors for vocalization in Xenopus laevis: hormonal regulation of sexual dimorphism. , 1986, Journal of neurobiology.

[39]  Paul Scherz,et al.  Defining brain wiring patterns and mechanisms through gene trapping in mice , 2001, Nature.

[40]  G. J. Vries Sex Differences in Neurotransmitter Systems , 1990, Journal of neuroendocrinology.

[41]  Laura L. Carruth,et al.  Sex chromosome genes directly affect brain sexual differentiation , 2002, Nature Neuroscience.

[42]  B. McEwen Sexual differentiation of the brain , 1981, Nature.

[43]  C. Wahlestedt,et al.  Isolation of sex-specific cDNAs from fetal mouse brain using mRNA differential display and representational difference analysis. , 1999, Brain research. Molecular brain research.

[44]  Anda Cornea,et al.  Sexual differentiation of projections from the principal nucleus of the bed nuclei of the stria terminalis , 2003, The Journal of comparative neurology.

[45]  L. Coolen,et al.  Neural activation following sexual behavior in the male and female rat brain , 1998, Behavioural Brain Research.

[46]  M. Konishi,et al.  Sexual differentiation of brain and behaviour , 1982, Trends in Neurosciences.

[47]  S. Levay,et al.  A difference in hypothalamic structure between heterosexual and homosexual men , 1991, Science.

[48]  Dick F. Swaab,et al.  A sex difference in the human brain and its relation to transsexuality , 1995, Nature.

[49]  S. Segovia,et al.  Lesions in the medial posterior region of the BST impair sexual behavior in sexually experienced and inexperienced male rats , 1995, Brain Research Bulletin.

[50]  W. Ovtscharoff,et al.  Sexual dimorphism of the bed nucleus of the stria terminalis and the amygdala. , 2000, Advances in anatomy, embryology, and cell biology.

[51]  G. Raisman,et al.  Sexual Dimorphism in the Preoptic Area of the Rat , 1971, Science.

[52]  Julia A. Taylor,et al.  Estrogen Receptor Function as Revealed by Knockout Studies: Neuroendocrine and Behavioral Aspects , 1997, Hormones and Behavior.

[53]  W. Byne,et al.  The interstitial nuclei of the human anterior hypothalamus: an investigation of sexual variation in volume and cell size, number and density , 2000, Brain Research.

[54]  R. Simerly Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. , 2002, Annual review of neuroscience.

[55]  Richard Axel,et al.  Visualizing an Olfactory Sensory Map , 1996, Cell.

[56]  S. Newman,et al.  Mating and agonistic behavior produce different patterns of Fos immunolabeling in the male Syrian hamster brain , 1995, Neuroscience.