Douglas Ashley Monks

Learn More
We created transgenic mice that overexpress WT androgen receptor (AR) exclusively in their skeletal muscle fibers. Unexpectedly, these mice display androgen-dependent muscle weakness and early death, show changes in muscle morphology and gene expression consistent with neurogenic atrophy, and exhibit a loss of motor axons. These features reproduce those(More)
Potential cellular targets of androgen action within skeletal muscle of the rat were determined by comparing the cellular distribution of androgen receptor (AR)-positive nuclei in the highly androgen-responsive levator ani (LA) muscle with that of the relatively androgen-unresponsive extensor digitorum longus (EDL) muscle. We found that androgen(More)
Ovarian hormones influence the physiology of the spinal cord through incompletely understood cellular mechanisms. To date, there has been little compelling evidence for progesterone receptors in spinal cord neurons. Using two antibodies specific for progesterone receptors in an immunohistochemical investigation, we now report the presence of(More)
In the adult hippocampus, gonadal steroids induce neural remodeling through cellular and molecular mechanisms that are largely unknown. The calcium-dependent cell adhesion molecule N-cadherin, which participates in the developmental organization of the nervous system, has recently been localized to hippocampal synapses and is suspected to participate in(More)
The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, bulbocavernosus and levator ani (BC/LA), form a sexually dimorphic neuromuscular circuit whose development and maintenance are androgen-dependent. The mechanisms whereby androgen regulates gene expression in the SNB of adult rats are largely unknown, although a retrograde influence from(More)
In rats, androgens in adulthood regulate the morphology of motoneurons in the spinal nucleus of the bulbocavernosus (SNB), including the size of their somata and the length of their dendrites. There are conflicting reports about whether androgens exert similar influences on SNB motoneurons in mice. We castrated or sham-operated C57BL6J mice at 90 days of(More)
We have recently reported that systemic androgens regulate adult N-cadherin (N-cad) expression in spinal motoneurons. However, the mechanism through which androgen mediates this effect remains undetermined. Androgen may act directly on motoneurons to regulate N-cad expression, or indirectly, via effects on androgen-sensitive afferent or efferent structures.(More)
Steroid receptor coactivator-1 (SRC-1) amplifies genomic steroid hormone signal transduction and has been implicated in steroid-mediated sexual differentiation of the mammalian nervous system. We investigated the possible effect of an SRC-1 null mutation on 2 morphological endpoints of androgenic signaling: the number and size of motoneurons within the(More)
Gonadal steroids influence the morphology and function of neurons in the adult spinal cord through cellular and molecular mechanisms that are largely unknown. The cadherins are cell adhesion molecules that participate in the formation and organization of the CNS during embryonic development, and recent evidence suggests that the cadherins continue to(More)
Kennedy Disease/Spinal Bulbar Muscular Atrophy (KD/SBMA) is a progressive neurodegenerative disease caused by genetic polyglutamine expansion of the androgen receptor. We have recently found that overexpression of wildtype androgen receptor in skeletal muscle of transgenic mice results in a KD/SBMA phenotype. This surprising result challenges the orthodox(More)