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Endocrinology, doi:10.1210/en.2008-1791
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Endocrinology Vol. 150, No. 8 3672-3679
Copyright © 2009 by The Endocrine Society

Androgen Regulates the Sexually Dimorphic Gastrin-Releasing Peptide System in the Lumbar Spinal Cord that Mediates Male Sexual Function

Hirotaka Sakamoto, Keiko Takanami, Damian G. Zuloaga, Ken-ichi Matsuda, Cynthia L. Jordan, S. Marc Breedlove and Mitsuhiro Kawata

Department of Anatomy and Neurobiology (H.S., K.T., K.-i.M., M.K.), Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan; and Program in Neuroscience (D.G.Z., C.L.J., S.M.B.), Departments of Psychology and Zoology, Michigan State University, East Lansing, Michigan 48824-1101

Address all correspondence and requests for reprints to: Hirotaka Sakamoto, Ph.D., Ushimado Marine Laboratory, Graduate School of Natural Science and Technology, Okayama University, Setouchi, Okayama 701-4303, Japan. E-mail: hsakomo{at}uml.okayama-u.ac.jp.

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.







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Copyright © 2009 by The Endocrine Society