EVOLUTION OF BRAIN-BEHAVIOR CONTROLLING MECHANISMS

Summary

Principal Investigator: DAVID P CREWS
Abstract: The goal of the proposed research is to elucidate the role of steroid hormones in controlling sexually dimorphic behaviors. Male-typical copulatory behaviors such as mounting and intromission are dependent on androgens in all vertebrates studied, but the mechanisms by which these hormones influence the brain and behavior are not well understood. Whiptail lizards of the genus Cnemidophorus enable a powerful comparative approach to understanding these mechanisms because some species are sexual, exhibiting the typical vertebrate pattern of sexually dimorphic behavior (estrogen-dependent receptivity in females and androgen-dependent mounting in males), and other species are all-female, reproducing clonally and exhibiting both male-like and female-like behavior, according to ovarian hormone levels. The experiments proposed involve C. inornatus, a typical sexual species, and C. uniparens, which is all-female. C. uniparens individuals, just like C. inornatus females, are receptive when their circulating estrogen levels are high, but unlike C. inornatus, they also exhibit the complete repertoire of male-typical copulatory behavior when presented with a receptive female during the periovulatory phase of the ovarian cycle when progesterone levels are high. This "pseudocopulatory" behavior can be evoked in the laboratory by administration of exogenous progesterone, and the operational goal of this research is to determine how progesterone is able to mimic the normal function of androgen in this way. Specific experiments will investigate how the progesterone receptor comes to be expressed in the preoptic area of the brain that is thought to mediate male-typical copulatory behavior, and in the process will yield information about the normal function of this area, as well as the developmental regulation of steroid hormone receptors. Other studies will elucidate the actions of androgens and progesterone on the neurotransmitters dopamine and nitric oxide, which are important components in the neural control of sexual behavior. This functional interchangeability of androgens and progestins has obvious fundamental implications for human health. All women normally experience fluctuating levels of progesterone, and millions of women use exogenous progestins. There is also a marked diurnal rhythm [in] progesterone levels in men, and progestins (usually in conjunction with testosterone) are beginning to be studied as a male contraceptive. The interaction of these progestins with the functions of other steroid hormones therefore warrants thorough investigation. From a scientific point of view, the hormonal control of sexual behavior is a particularly tractable model for elucidating the way in which particular genes, expressed in particular neural circuits, can affect specific behaviors, because the stimuli and behaviors involved are simple, the brain areas involved are well characterized, and the relationship between hormones and genes is comparatively well understood.
Funding Period: 1986-09-01 - 2010-11-30
more information: NIH RePORT

Top Publications

  1. pmc Binary outputs from unitary networks
    David Crews
    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA
    Integr Comp Biol 53:888-94. 2013
  2. pmc Androgens coordinate neurotransmitter-related gene expression in male whiptail lizards
    L A O'Connell
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA
    Genes Brain Behav 11:813-8. 2012
  3. pmc Epigenetic modifications of brain and behavior: theory and practice
    David Crews
    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA
    Horm Behav 59:393-8. 2011
  4. pmc Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards
    Lauren A O'Connell
    Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States
    Gen Comp Endocrinol 171:64-74. 2011
  5. ncbi Neuronal nitric oxide synthase as a substrate for the evolution of pseudosexual behaviour in a parthenogenetic whiptail lizard
    L A O'Connell
    Institute for Cell and Molecular Biology, Austin, TX, USA
    J Neuroendocrinol 23:244-53. 2011
  6. pmc Analyzing the coordinated gene network underlying temperature-dependent sex determination in reptiles
    Christina M Shoemaker
    Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78705, United States
    Semin Cell Dev Biol 20:293-303. 2009
  7. pmc Steroid signaling and temperature-dependent sex determination-Reviewing the evidence for early action of estrogen during ovarian determination in turtles
    Mary Ramsey
    Section of Integrative Biology, University of Texas, 2400 Speedway, Austin, TX 78712, United States
    Semin Cell Dev Biol 20:283-92. 2009
  8. pmc Testosterone stimulates mounting behavior and arginine vasotocin expression in the brain of both sexual and unisexual whiptail lizards
    K D Hillsman
    Section of Integrative Biology, University of Texas, Austin, Tex 78712, USA
    Sex Dev 1:77-84. 2007
  9. pmc Regulation of pseudosexual behavior in the parthenogenetic whiptail lizard, Cnemidophorus uniparens
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA
    Endocrinology 149:4622-31. 2008
  10. pmc Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA
    Brain Res 1253:129-38. 2009

Scientific Experts

  • DAVID P CREWS
  • S C Woolley
  • M B Hawkins
  • William S Modi
  • Brian George Dias
  • L A O'Connell
  • Nicholas S R Sanderson
  • Lauren A O'Connell
  • Mary Ramsey
  • Christina M Shoemaker
  • K D Hillsman
  • N S R Sanderson
  • M M Mitchell
  • H A Hofmann
  • Sagar B Patel
  • Jeremy D O'Connell
  • Bryan J Matthews
  • B J Matthews
  • Sonia Grace Chin
  • Zifei Zhou
  • Brandon Le
  • David Rushworth
  • Ramona Sousan Ataya
  • N S Sanderson
  • Jun Zhao
  • B D Le
  • Erik Weissler

Detail Information

Publications22

  1. pmc Binary outputs from unitary networks
    David Crews
    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA
    Integr Comp Biol 53:888-94. 2013
    ..A perspective that integrates these different properties are presented here. ..
  2. pmc Androgens coordinate neurotransmitter-related gene expression in male whiptail lizards
    L A O'Connell
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA
    Genes Brain Behav 11:813-8. 2012
    ..This also suggests that the proposed evolutionarily ancient reward system that reinforces sexual behavior in amniote vertebrates extends to reptiles...
  3. pmc Epigenetic modifications of brain and behavior: theory and practice
    David Crews
    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA
    Horm Behav 59:393-8. 2011
    ..Lastly, it seems intuitive that germline- and context-dependent epigenetic modifications interact, resulting in the individual variation observed in behaviors, but until now this hypothesis has never been tested experimentally...
  4. pmc Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards
    Lauren A O'Connell
    Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States
    Gen Comp Endocrinol 171:64-74. 2011
    ..Our results significantly extend our understanding of progesterone modulation in the reptilian brain and support the important role of the nuclear progesterone receptor in modulating sexual behavior in reptiles and across vertebrates...
  5. ncbi Neuronal nitric oxide synthase as a substrate for the evolution of pseudosexual behaviour in a parthenogenetic whiptail lizard
    L A O'Connell
    Institute for Cell and Molecular Biology, Austin, TX, USA
    J Neuroendocrinol 23:244-53. 2011
    ..These data suggest that a polymorphism in progesterone sensitivity in the sexual ancestor reflects a differential regulation of nNOS and may account for the male-typical behaviour in unisexual whiptail lizards...
  6. pmc Analyzing the coordinated gene network underlying temperature-dependent sex determination in reptiles
    Christina M Shoemaker
    Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78705, United States
    Semin Cell Dev Biol 20:293-303. 2009
    ..We discuss some of the problems encountered unraveling this network, pose potential solutions, and suggest rewarding future directions of research...
  7. pmc Steroid signaling and temperature-dependent sex determination-Reviewing the evidence for early action of estrogen during ovarian determination in turtles
    Mary Ramsey
    Section of Integrative Biology, University of Texas, 2400 Speedway, Austin, TX 78712, United States
    Semin Cell Dev Biol 20:283-92. 2009
    ..Localized estrogen production facilitates ovarian development while inhibiting male-specific gene expression. At male-producing temperatures aromatase is not upregulated, thereby allowing testis development...
  8. pmc Testosterone stimulates mounting behavior and arginine vasotocin expression in the brain of both sexual and unisexual whiptail lizards
    K D Hillsman
    Section of Integrative Biology, University of Texas, Austin, Tex 78712, USA
    Sex Dev 1:77-84. 2007
    ..Testosterone treatment generally increased AVT abundance, except in lab-reared parthenoforms, in which testosterone treatment was the least effective in inducing male-like copulatory behavior...
  9. pmc Regulation of pseudosexual behavior in the parthenogenetic whiptail lizard, Cnemidophorus uniparens
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA
    Endocrinology 149:4622-31. 2008
    ..This study illuminates how male- and female-typical sexual behaviors share common neural circuits, and that 5-HT regulates these naturally complementary, and mutually exclusive, behaviors...
  10. pmc Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA
    Brain Res 1253:129-38. 2009
    ..This study also supports the idea that non-gonadal sources of steroid hormones locally produced in behaviorally relevant brain loci are central to the mediation of behavioral output...
  11. pmc Epigenetics and its implications for behavioral neuroendocrinology
    David Crews
    Section of Integrative Biology and Center of Behavioral Neuroendocrinology, University of Texas at Austin, Austin, TX 78712, USA
    Front Neuroendocrinol 29:344-57. 2008
    ..This work raises the question of how events in generations past can have consequences at both the mechanistic, behavioral, and ultimately evolutionary levels...
  12. pmc Preoptic neuronal nitric oxide synthase induction by testosterone is consistent with a role in gating male copulatory behavior
    Nicholas S R Sanderson
    Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA
    Eur J Neurosci 27:183-90. 2008
    ..Results are consistent with transcriptional up-regulation of nNOS by testosterone and a central role for the enzyme in mediating hormonal gating of copulatory behavior...
  13. ncbi The nitric oxide synthase inhibitor L-NAME suppresses androgen-induced male-like pseudocopulatory behavior in whiptail lizards
    Nicholas S R Sanderson
    Institute for Neuroscience, University of Texas at Austin, 78712, USA
    Brain Res 1052:236-9. 2005
    ..The deficit was principally in mounting, suggesting that sexual motivational systems were affected, rather than consummatory mechanisms...
  14. ncbi Evolution of neuroendocrine mechanisms that regulate sexual behavior
    David Crews
    Ashbel Smith Professor of Zoology and Psychology, Section of Integrative Biology, University of Texas, Austin, TX 78712, USA
    Trends Endocrinol Metab 16:354-61. 2005
    ....
  15. ncbi Sex chromosomes and sex determination in reptiles
    William S Modi
    SAIC Frederick, National Cancer Institute, Core Genotyping Facility, 8717 Grovemont Circle, Gaithersburg, MD 20877, USA
    Curr Opin Genet Dev 15:660-5. 2005
    ..This information should contribute extensively toward a general understanding of the genetic control of development in amniotes...
  16. ncbi Genotype differences in behavior and tyrosine hydroxylase expression between wild-type and progesterone receptor knockout mice
    Sarah C Woolley
    Section of Integrative Biology, University of Texas at Austin, TX, USA
    Behav Brain Res 167:197-204. 2006
    ....
  17. ncbi Epigenetics, evolution, endocrine disruption, health, and disease
    David Crews
    Section of Integrative Biology, 2400 Speedway, University of Texas, Austin, Texas 78712, USA
    Endocrinology 147:S4-10. 2006
    ..We suggest a perspective for exploring and ultimately coming to understand diseases that may have environmental or endocrine origins...
  18. pmc Serotonergic modulation of male-like pseudocopulatory behavior in the parthenogenetic whiptail lizard, Cnemidophorus uniparens
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA
    Horm Behav 50:401-9. 2006
    ....
  19. pmc Testosterone induction of male-typical sexual behavior is associated with increased preoptic NADPH diaphorase and citrulline production in female whiptail lizards
    N S R Sanderson
    Institute for Neuroscience, University of Texas at Austin, 1 University Station C0930, Austin, Texas 78712, USA
    J Neurobiol 66:1156-63. 2006
    ..This is the first demonstration that not only is NOS up-regulated by testosterone, but NOS thus up-regulated is activated during male-typical copulatory behavior...
  20. pmc From gene networks underlying sex determination and gonadal differentiation to the development of neural networks regulating sociosexual behavior
    David Crews
    Section of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA
    Brain Res 1126:109-21. 2006
    ....
  21. ncbi Effect of incubation temperature and androgens on dopaminergic activity in the leopard gecko, Eublepharis macularius
    Brian George Dias
    Institute for Neuroscience, University of Texas at Austin, Austin, Texas, USA
    Dev Neurobiol 67:630-6. 2007
    ..These data indicate that both the embryonic environment as well as the circulating hormonal milieu can modulate neurochemistry, which might in turn be a basis for individual variation in behavior...
  22. pmc The distributions of the duplicate oestrogen receptors ER-beta a and ER-beta b in the forebrain of the Atlantic croaker (Micropogonias undulatus): evidence for subfunctionalization after gene duplication
    M B Hawkins
    Marine Science Institute, University of Texas at Austin, Port Aransas, TX 78373, USA
    Proc Biol Sci 272:633-41. 2005
    ....