ESTROGENIC EFFECTS IN ANDROGEN SENSITIVE MOTONEURONS

Summary

Principal Investigator: DALE SENGELAUB
Abstract: DESCRIPTION: Estrogen is considered to be the primary metabolite responsible for the differentiation of sexually dimorphic brain regions. In contrast, the development of sexually dimorphic nuclei in the spinal cord has been considered to be regulated strictly by androgens. Testing the validity and limitations of this apparent dichotomy in the critical forms of steroid hormones involved in sexual differentiation of the nervous system and potential differences in their site of action is the focus of this proposal. Using a simple hormone-sensitive neuromuscular system in the rat spinal cord, three different features of this system will be examined: aspects of motoneuron morphology (histochemistry), distribution of critical enzymes (immunocytochemistry), and neuromuscular function (electrophysiology). Synergistic effects of estrogen and androgen, the necessity of estrogen availability, the role of supraspinal and local interneuronal, estrogen-sensitive afferents, and the effects of naturally occurring estrogen levels in morphological development will be assessed. Because the transient expression of aromatase has been reported in a variety of developing neural structures, postnatal spinal cords will be assayed for the presence of aromatase. The role of estrogen in regulating the development of gap junctions, which are common in these motoneurons, will also be examined. Changes in motoneuron excitability during development are likely responsible for the onset of spinally mediated reflexes, and the role of estrogen and androgen in the development of several functional properties of these hormone-sensitive motoneurons will be assessed. Because recent evidence suggests that estrogen is in fact involved in spinal cord masculinization, these studies may help in unifying our understanding of the process of sexual differentiation across the developing mammalian central nervous system.
Funding Period: 1998-03-01 - 2004-02-29
more information: NIH RePORT

Top Publications

  1. ncbi NMDA receptor binding declines differentially in three spinal motor nuclei during postnatal development
    Tom Verhovshek
    Program in Neural Science, Department of Psychology, Indiana University, Bloomington, IN 47405, USA
    Neurosci Lett 384:122-6. 2005
  2. pmc Critical period for estrogen-dependent motoneuron dendrite growth is coincident with ERα expression in target musculature
    Lauren M Rudolph
    Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA
    Dev Neurobiol 73:72-84. 2013
  3. pmc Castration-induced upregulation of muscle ERα supports estrogen sensitivity of motoneuron dendrites in a sexually dimorphic neuromuscular system
    Lauren M Rudolph
    Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, Indiana, 47405
    Dev Neurobiol 73:921-35. 2013
  4. ncbi Maternal licking influences dendritic development of motoneurons in a sexually dimorphic neuromuscular system
    Kathryn M Lenz
    Department of Psychological and Brain Sciences and Program in Neuroscience, 1101 E 10th Street, Indiana University, Bloomington, IN 47405, USA
    Brain Res 1092:87-99. 2006
  5. ncbi Estrogenic support of motoneuron dendritic growth via the neuromuscular periphery in a sexually dimorphic motor system
    Ari S Nowacek
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, 47405, USA
    J Neurobiol 66:962-76. 2006
  6. pmc The spinal nucleus of the bulbocavernosus: firsts in androgen-dependent neural sex differences
    Dale R Sengelaub
    Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
    Horm Behav 53:596-612. 2008
  7. pmc Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system
    Tom Verhovshek
    Department of Psychological and Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, Indiana 47405, USA
    Dev Neurobiol 70:206-21. 2010

Scientific Experts

  • DALE SENGELAUB
  • Lauren M Rudolph
  • Tom Verhovshek
  • Kathryn M Lenz
  • Ari S Nowacek
  • Melissa A Sergent
  • Katherine E Buckley
  • Cara L Wellman

Detail Information

Publications7

  1. ncbi NMDA receptor binding declines differentially in three spinal motor nuclei during postnatal development
    Tom Verhovshek
    Program in Neural Science, Department of Psychology, Indiana University, Bloomington, IN 47405, USA
    Neurosci Lett 384:122-6. 2005
    ....
  2. pmc Critical period for estrogen-dependent motoneuron dendrite growth is coincident with ERα expression in target musculature
    Lauren M Rudolph
    Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA
    Dev Neurobiol 73:72-84. 2013
    ..These data suggest that the transient ERα expression in target muscle could potentially define the critical period for estrogen-dependent dendrite growth in SNB motoneurons...
  3. pmc Castration-induced upregulation of muscle ERα supports estrogen sensitivity of motoneuron dendrites in a sexually dimorphic neuromuscular system
    Lauren M Rudolph
    Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, Indiana, 47405
    Dev Neurobiol 73:921-35. 2013
    ....
  4. ncbi Maternal licking influences dendritic development of motoneurons in a sexually dimorphic neuromuscular system
    Kathryn M Lenz
    Department of Psychological and Brain Sciences and Program in Neuroscience, 1101 E 10th Street, Indiana University, Bloomington, IN 47405, USA
    Brain Res 1092:87-99. 2006
    ....
  5. ncbi Estrogenic support of motoneuron dendritic growth via the neuromuscular periphery in a sexually dimorphic motor system
    Ari S Nowacek
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, 47405, USA
    J Neurobiol 66:962-76. 2006
    ..Thus, estrogens may act by an indirect action in the neuromuscular periphery to support SNB dendritic growth...
  6. pmc The spinal nucleus of the bulbocavernosus: firsts in androgen-dependent neural sex differences
    Dale R Sengelaub
    Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
    Horm Behav 53:596-612. 2008
    ..We also describe new data on neurotherapeutic effects of androgens on SNB motoneurons after injury in adulthood...
  7. pmc Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system
    Tom Verhovshek
    Department of Psychological and Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, Indiana 47405, USA
    Dev Neurobiol 70:206-21. 2010
    ..Together, these results suggest that the maintenance of adult motoneuron or muscle morphology is strictly mediated by androgens...