Direct androgenic regulation of calcitonin gene-related peptide expression in motoneurons of rats with mosaic androgen insensitivity.
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 the BC/LA muscles has been suggested to underlie the suppression of calcitonin gene-related peptide (CGRP) expression observed in SNB motoneurons after systemic androgen treatment. A mosaic paradigm was used to determine the site of action of androgen in the regulation of CGRP expression in SNB motoneurons. As a consequence of random X chromosome inactivation, androgenized female rats heterozygous for the tfm androgen receptor (AR) mutation (XwtXtfm-mosaics) express a mosaic of androgen-sensitive and androgen-insensitive motoneurons in the SNB, whereas the BC/LA target musculature appears to be uniformly sensitive to androgens. In adult mosaics, testosterone administration resulted in a reduction in the proportion of androgen-sensitive cells expressing CGRP, whereas no such reduction was observed in the androgen-insensitive population, indicating that neuronal AR plays an essential role in the neuromuscular regulation of CGRP expression in these motoneurons. This provides the first in vivo demonstration of AR regulation of gene expression unambiguously localized to a neuronal population.
Monks
D A
DA
Department of Psychology, Simon Fraser University, Burnaby, British Columbia, V5A 1S6 Canada.
Vanston
C M
CM
Watson
N V
NV
D013734:Androgen-Insensitivity Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000728:Androgens / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006579:Heterozygote; D007150:Immunohistochemistry; D008297:Male; D008954:Models, Biological; D009030:Mosaicism / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D051381:Rats; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D011944:Receptors, Androgen; D013739:Testosterone; D015740:Calcitonin Gene-Related Peptide