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Review
. 2008 May;53(5):716-28.
doi: 10.1016/j.yhbeh.2008.01.014. Epub 2008 Feb 15.

Androgen regulation of axon growth and neurite extension in motoneurons

Keith N Fargo  1 , Mariarita Galbiati, Eileen M Foecking, Angelo Poletti, Kathryn J Jones
Affiliations
Review

Androgen regulation of axon growth and neurite extension in motoneurons

Keith N Fargo et al. Horm Behav. 2008 May.

Abstract

Androgens act on the CNS to affect motor function through interaction with a widespread distribution of intracellular androgen receptors (AR). This review highlights our work on androgens and process outgrowth in motoneurons, both in vitro and in vivo. The actions of androgens on motoneurons involve the generation of novel neuronal interactions that are mediated by the induction of androgen-dependent neurite or axonal outgrowth. Here, we summarize the experimental evidence for the androgenic regulation of the extension and regeneration of motoneuron neurites in vitro using cultured immortalized motoneurons, and axons in vivo using the hamster facial nerve crush paradigm. We place particular emphasis on the relevance of these effects to SBMA and peripheral nerve injuries.

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Figures

Figure 1
Figure 1
Differential interference contrast photomicrograph of MN hybrid cells transfected with AR and treated for 48 hours with either 100 nM DHT or vehicle control. Note that DHT-treated cells have longer neurites (arrows). (After DeLucia et al., 2007.)
Figure 2
Figure 2
Confocal microscopy image of NSC34/mAR cells expressing the mutant SBMA AR and treated with testosterone. Several SBMA AR neuropil aggregates have formed (green), along with an accumulation of the motor protein kinesin (red). Scale bar = 20 μm. Inset: closer view of a neurite. (After Piccioni et al, 2002.)
Figure 3
Figure 3
Outgrowth distances from the point of nerve crush to the leading edge of the growing axons at 4 days, 5 days, and 7 days following injury in castrated male hamsters and castrated male hamsters given systemic testosterone treatment. Circles represent means and vertical lines represent SEMs. * = p < .05. Diagonal lines represent extrapolation of the data. Note that the data extrapolate to approximately 2 days post-injury for the zero outgrowth distance. This time point corresponds both to the androgen-induced spike in neuritin mRNA levels (see Section 3.4) and to the earliest time point at which androgen treatment augments tubulin upregulation following axotomy (Jones and Oblinger, 1994; Jones et al., 1999b). (After Kujawa et al., 1991.)
Figure 4
Figure 4
Neuritin mRNA levels in AR− and AR+ cultured MN cells, treated with either 100 nM DHT (filled bars) or vehicle only (open bars). DHT treatment doubled neuritin mRNA levels, but only in AR+ cells. Bars heights represent means (± SEM).
Figure 5
Figure 5
Neuritin mRNA levels in axotomized hamsters (open bars) and axotomized hamsters treated with testosterone (black bars) at 6 hours and 1, 2, 4, 6, and 7 days post-axotomy. Also shown are axotomized hamsters treated with both testosterone and flutamide for 2 days following axotomy (gray bar). Neuritin mRNA levels are displayed as the percent difference between the axotomized side and the control side within each animal. Testosterone caused a dramatic increase in neuritin mRNA levels 2 days post-axotomy; however, this increase was completely prevented by flutamide treatment. Bars heights represent means (± SEM).
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References

    1. Abdullah AAR, Trifiro MA, Panetraymond V, Alvarado C, Detourreil S, Frankel D, Schipper HM, Pinsky L. Spinobulbar muscular atrophy - polyglutamine-expanded androgen receptor is proteolytically resistant in vitro and processed abnormally in transfected cells. Hum Mol Genet. 1998;7:379–384. - PubMed
    1. Al-Shamma HA, Arnold AP. Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons. Proc Natl Acad Sci U S A. 1997;94:1521–1526. - PMC - PubMed
    1. Avila DM, Allman DR, Gallo JM, McPhaul MY. Androgen receptors containing expanded polyglutamine tracts exhibit progressive toxicity when stably expressed in the neuroblastoma cell line, SH-SY 5Y. Exp Biol Med. 2003;228:982–990. - PubMed
    1. Bardo S, Cavazzini MG, Emptage N. The role of the endoplasmic reticulum Ca2+ store in the plasticity of central neurons. Trends Pharmacol Sci. 2006;27:78–84. - PubMed
    1. Belsham DD, Evangelou A, Roy D, Vinh Le D, Brown TJ. Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alpha-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons. Endocrinology. 1998;139:1108–1114. - PubMed