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Androgen regulates the sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord that mediates male sexual function.

Abstract
A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate male sexual reflexes such as erection and ejaculation. Because these reflexes are androgen dependent, we asked whether manipulating levels of androgen in adult rats would affect GRP expression in this spinal center. We found that castration resulted, 28 d later, in a profound decrease in the expression of GRP in the spinal cord, as reflected in immunocytochemistry and competitive ELISA for the protein as well as real-time quantitative PCR for the transcript. These effects were prevented if the castrates were treated with testosterone propionate. Genetically male (XY) rats with the dysfunctional testicular feminization allele for the androgen receptor (AR) displayed GRP mRNA and protein levels in the spinal cord similar to those of females, indicating that androgen normally maintains the system through AR. We saw no effect of castration or the testicular feminization allele on expression of the receptor for GRP in the spinal cord, but castration did reduce expression of AR transcripts within the spinal cord as revealed by real-time quantitative PCR and Western blots. Taken together, these results suggest that androgen signaling plays a pivotal role in the regulation of GRP expression in male lumbar spinal cord. A greater understanding of how androgen modulates the spinal GRP system might lead to new therapeutic approaches to male sexual dysfunction.
AuthorsHirotaka Sakamoto, Keiko Takanami, Damian G Zuloaga, Ken-ichi Matsuda, Cynthia L Jordan, S Marc Breedlove, Mitsuhiro Kawata
JournalEndocrinology (Endocrinology) Vol. 150 Issue 8 Pg. 3672-9 (Aug 2009) ISSN: 1945-7170 [Electronic] United States
PMID19359382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Androgens
  • Receptors, Androgen
  • Receptors, Bombesin
  • Testosterone
  • Gastrin-Releasing Peptide
Topics
  • Androgen-Insensitivity Syndrome (metabolism)
  • Androgens (metabolism, physiology)
  • Animals
  • Blotting, Western
  • Castration
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Gastrin-Releasing Peptide (genetics, metabolism)
  • Immunohistochemistry
  • Male
  • Polymerase Chain Reaction
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, Androgen (genetics, metabolism, physiology)
  • Receptors, Bombesin (metabolism)
  • Sexual Development (physiology)
  • Spinal Cord (metabolism)
  • Testosterone (blood)

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