Androgen receptor mRNA regulation in adult male and female hamster facial motoneurons: effects of axotomy and exogenous androgens

Larkowski, Troy D.; Drengler, Susan M.; Tanzer, Lisa; Jones, Kathryn J.

doi:10.1002/1097-4695(200012)45:4<207::aid-neu2>3.0.co;2-v

Cited by 13 publications

(16 citation statements)

References 32 publications

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“…There is a known sex difference in androgen receptor protein in rat facial motoneuron somata, with males having more [165]. Interestingly, while testosterone treatment of castrated males increases androgen receptor mRNA in facial motoneuron somata, this effect is completely blocked by axotomy [31,89]. Axotomy-induced downregulation of androgen receptor has also been found in spinal motoneurons [92,157].…”

Section: Androgen-enhanced Nerve Regenerationmentioning

confidence: 99%

Neuroprotective actions of androgens on motoneurons

Fargo

Foecking

Jones

et al. 2009

Frontiers in Neuroendocrinology

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Androgens have a variety of protective and therapeutic effects in both the central and peripheral nervous systems. Here we review these effects as they related specifically to spinal and cranial motoneurons. Early in development, androgens are critical for the formation of important neuromuscular sex differences, decreasing the magnitude of normally occurring cell death in select motoneuron populations. Throughout the lifespan, androgens also protect against motoneuron death caused by axonal injury. Surviving motoneurons also display regressive changes to their neurites as a result of both direct axonal injury and loss of neighboring motoneurons. Androgen treatment enhances the ability of motoneurons to recover from these regressive changes and regenerate both axons and dendrites, restoring normal neuromuscular function. Androgens exert these protective effects by acting through a variety of molecular pathways. Recent work has begun to examine how androgen treatment can interact with other treatment strategies in promoting recovery from motoneuron injury. Keywords motoneurons; androgens; axotomy; neuroprotection; cell death; sex differences; nerve regeneration; dendrites; testosterone; steroids From cellular and molecular perspectives, the consequences of gonadal steroid action in the nervous system include profound trophic effects on target neurons. During development, gonadal steroids are involved in the establishment of sex differences in neural structure and organization that underlie sex differences in behavior [122], promoting the differentiation of a masculine pattern of neural organization [3,111]. For example, androgens have been shown to exert a potent influence on the determination of sex differences in neuron number [116,

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Section: Androgen-enhanced Nerve Regenerationmentioning

confidence: 99%

Neuroprotective actions of androgens on motoneurons

Fargo

Foecking

Jones

et al. 2009

Frontiers in Neuroendocrinology

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“…Hence, the activation of this receptor could be involved in the control of the locomotor responses. The physiological functions of AR in the spinal cord have been analysed in several studies performed in rodents, in which AR is expressed at high levels in somatic motor neurones localized in the trigeminal, facial, ambiguous and hypoglos-sal nuclei (Matsumoto et al 1988;Freeman et al 1995;Drengler et al 1996;Lumbroso et al 1996;Matsumoto 1997;Larkowski et al 2000;Yu and McGinnis 2001). By acting on these structures, androgens promote the regrowth of the corresponding peripheral nerves after resection, enhancing the rate of axonal elongation towards their targets in the hypoglossal, facial and sciatic nerves (Yu 1989;Kujawa et al 1993).…”

mentioning

confidence: 99%

Androgen‐induced neurite outgrowth is mediated by neuritin in motor neurones

Marron

Guerini

Rusmini

et al. 2004

Journal of Neurochemistry

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In the brain, the spinal cord motor neurones express the highest levels of the androgen receptor (AR). Experimental data have suggested that neurite outgrowth in these neurones may be regulated by testosterone or its derivative 5a-dihydrotestosterone (DHT), formed by the 5a-reductase type 2 enzyme. In this study we have produced and characterized a model of immortalized motor neuronal cells expressing the mouse AR (mAR) [neuroblastoma-spinal cord (NSC) 34/mAR] and analysed the role of androgens in motor neurones. Androgens either activated or repressed several genes; one has been identified as the mouse neuritin, a protein responsible for neurite elongation. Real-time PCR analysis has shown that the neuritin gene is expressed in the basal condition in immortalized motor neurones and is selectively upregulated by androgens in NSC34/mAR cells; the DHT effect is counteracted by the anti-androgen Casodex. Moreover, DHT induced neurite outgrowth in NSC34/mAR, while testosterone was less effective and its action was counteracted by the 5a-reductase type 2 enzyme inhibitor finasteride. Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration.

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“…How and where androgens exert this influence remain unclear. The motoneurons are one potential target, but recent evidence indicates that expression of AR in motoneurons is severely down‐regulated in response to axotomy (al‐Shamma and Arnold, 1995; Lubischer and Arnold, 1995; Larkowski et al, 2000). This observation challenges the idea that androgens act via the motoneurons to enhance the growth of their axons.…”

Section: Discussionmentioning

confidence: 99%

“…If androgenic hormones exert beneficial effects on peripheral nerves, where and how do they do so? Androgen receptors (ARs) are present in the motoneurons contributing axons to the facial, hypoglossal (Drengler et al, 1997; Larkowski et al, 2000; Yu and McGinnis, 2001), and sciatic (Breedlove and Arnold, 1983; Jordan et al, 1991, 1997; Freeman et al, 1995) nerves. Moreover, ARs are also located in their target musculatures (Dube et al, 1976; Dionne et al, 1979; Yu and McGinnis, 1986).…”

mentioning

confidence: 99%

Androgen receptor messenger RNA and protein in adult rat sciatic nerve: Implications for site of androgen action

Jordan

Price

2002

J of Neuroscience Research

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Gonadal androgens exert a wide variety of effects on several neuromuscular systems, including controlling the developmental fate of motoneurons and neuromuscular synapses and promoting the growth of adult dendrites and axons. Paramount in understanding the molecular mechanisms behind androgen action is determining where androgen acts; does androgen act directly or indirectly on cells to change their fate and function? One step toward answering this question has been to determine which cells express androgen receptors (ARs). Motoneurons and skeletal muscles both have ARs and are, therefore, potential sites of androgen action. Recent evidence indicates that the sciatic nerve in rats also contains AR mRNA (Magnaghi et al. [1999] Brain Res. Mol. Brain Res. 70:36-44), although which cell type expresses ARs remains unanswered. In this study, we explored the question of which cell populations in the rat sciatic nerve express ARs. Using immunocytochemistry and reverse transcriptase-PCR, we confirmed the presence of AR protein and mRNA in sciatic nerve from adult rats and found a sex difference, favoring males, in the number of cell nuclei immunopositive for AR. This difference was not due to a sex difference in the overall number of cell nuclei. We also found a difference favoring males in AR mRNA, evidence also suggesting that AR expression is higher in males than in females. Results from double-immmunolabeling experiments in sciatic nerve from adult males suggest that, within the endoneurial compartment, endoneurial fibroblasts stain prominently for AR, with some endothelial cells also AR(+). Although Schwann cells showed light AR immunostaining, this staining is apparently nonspecific. We conclude that cells within peripheral nerve have ARs and may, therefore, mediate some of the effects of androgens on neuromuscular systems.

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Androgen receptor mRNA regulation in adult male and female hamster facial motoneurons: effects of axotomy and exogenous androgens

Cited by 13 publications

References 32 publications

Neuroprotective actions of androgens on motoneurons

Neuroprotective actions of androgens on motoneurons

Androgen‐induced neurite outgrowth is mediated by neuritin in motor neurones

Androgen receptor messenger RNA and protein in adult rat sciatic nerve: Implications for site of androgen action

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