Androgens Prevent Normally Occurring Cell Death in a Sexually Dimorphic Spinal Nucleus

Nordeen, Ernest J.; Nordeen, Kathy W.; Sengelaub, Dale R.; Arnold, Arthur P.

doi:10.1126/science.4023706

Cited by 451 publications

(278 citation statements)

References 15 publications

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“…The LA is innervated by the axons of motoneurons in the so-called spinal nucleus of the bulbocavernosus (SNB; Breedlove and Arnold, 1980). These motoneurons are able to accumulate androgens during the perinatal period, a property that enhances their survival in the male and thus ensuring the sexual dimorphism of the perineal striated muscle complex of which the LA is a component (Nordeen et al, 1985;Jordan et al, 1991). There is no report, however, that the SNB retains its androgen sensitivity beyond the first four postnatal weeks.…”

Section: Discussionmentioning

confidence: 99%

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

Nnodim

2001

Anat. Rec.

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Denervation stimulates quiescent satellite cells in skeletal muscle to reenter the cell cycle. In the androgen-sensitive rat levator ani muscle (LA), this mitotic response to loss of neural input fails to occur in castrated animals. To elucidate the role of androgens in denervation-induced satellite cell proliferation, the denervated LA of castrated rats (Group A) was compared with that of animals infixed with testosterone implants after castration (Group B). Mean myofiber cross-sectional areas (Group A: 362.95 m 2 Ϯ 27.74; Group B: 403.13 m 2 Ϯ 53.87) and linear nuclear densities (Group A: 74.07 mm Ϫ1 Ϯ 17.58; Group B: 104.13 mm Ϫ1 Ϯ 4.06) were similar (P Ͼ 0.05) in both groups. The androgen-deprived myofibers of Group A, however, had a significantly lower nuclear content (271.0 Ϯ 74.91 vs. 1,285.80 Ϯ 81.74 in Group B; P Ͻ 0.05) on account of their considerably shorter mean length (3.44 mm Ϯ 0.29 vs. 12.31 mm Ϯ 0.92 in Group B; P Ͻ 0.05). The proportional representation of satellite cells in hormone-replaced, denervated muscle was more than twice that in the untreated group (Group B: 5.15 Ϯ 0.83% vs. Group A: 2.28 Ϯ 0.23%; P Ͻ 0.05). In absolute terms, the satellite cell number in Group B was approximately an order of magnitude greater than in Group A (408.4 ϫ 10 3 vs. 38.08 ϫ 10 3 ). The results confirm the absence of testosterone as the factor responsible for the inability of satellite cells in the LA of castrated rats to respond mitotically to the withdrawal of neural input after denervation.

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Section: Discussionmentioning

confidence: 99%

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

Nnodim

2001

Anat. Rec.

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“…Adult males have many more SNB motoneurons than do females (Breedlove and Arnold, 1980). Previous studies have mapped the development of this sex difference in SNB motoneuron number (Nordeen et al, 1985;Sengelaub and Arnold, 1986). On embryonic day 18 (El 8; day of birth = E23) the number of cells in the SNB is similar in males and females, but small relative to later values.…”

Section: Ciliary Neurotrophicmentioning

confidence: 99%

“…The rat spinal nucleus of the bulbocavernosus (SNB) is exceptional, however, in that cell death in the SNB occurs primarily during the first postnatal week (Nordeen et al, 1985). SNB motoneurons reside in the ventromedial lumbar spinal cord and the majority of motoneurons in this nucleus innervate the bulbocavernosus (BC) and levator ani (LA), two sexually dimorphic, striated muscles active during copulation (Sachs, 1982;Wallach and Hart, 1983).…”

Section: Ciliary Neurotrophicmentioning

confidence: 99%

Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats

et al. 1993

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Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991). Because receptors for CNTF are expressed in both motoneurons and their target muscles (Davis et al., 1991; lp et al., 1993), both tissues are potential sites of CNTF action in development. We examined the ability of CNTF to prevent the degeneration of a neuromuscular system in developing female rats. The death of motoneurons in the spinal nucleus of the bulbocavernosus (SNB) extends postnatally and is sexually dimorphic, with many more motoneurons dying in females than in males. The bulbocavernosus (BC), a target muscle of SNB motoneurons, also degenerates postnatally in females. Female rats treated with daily injections of 1 microgram CNTF from embryonic day 22 through postnatal day 3 (P3) had 70% more SNB motoneurons on P4 than did control animals, and the number of pyknotic profiles in the SNB area was markedly reduced by CNTF. In addition, the degeneration of the BC was completely prevented by CNTF treatment of perinatal female rats. These results demonstrate that CNTF can preserve mammalian motoneurons from developmental death, but also suggest that the sparing effect of CNTF on motoneurons in vivo may be a secondary consequence of effects on target muscles.

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“…In vivo, androgens also promote the survival of motoneurons in both the spinal cord (SNB motoneurons; Breedlove and Arnold, 1983a,b;Nordeen et al, 1985) and brainstem (facial motoneurons; Huppenbauer et al, 2005;Tetzlaff et al, 2006). While the androgen-dependent survival of SNB motoneurons during development is traditionally thought of as being mediated by their target muscles (Kurz et al, 1992;Johansen et al, 2004), androgens are capable of preventing the death of facial motoneurons that have been disconnected from their target muscles by axotomy (Huppenbauer et al, 2005;Tetzlaff et al, 2006).…”

Section: Future Directionsmentioning

confidence: 99%

Androgen regulation of axon growth and neurite extension in motoneurons

Fargo

Galbiati

Foecking

et al. 2008

Hormones and Behavior

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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 androgendependent 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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Androgens Prevent Normally Occurring Cell Death in a Sexually Dimorphic Spinal Nucleus

Cited by 451 publications

References 15 publications

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats

Androgen regulation of axon growth and neurite extension in motoneurons

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