Sexually dimorphic gastrin releasing peptide system in the spinal cord controls male reproductive functions

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Neurons in the upper lumbar spinal cord project axons containing gastrin-releasing peptide (GRP) to innervate lower lumbar regions controlling erection and ejaculation. This system is vestigial in female rats and in males with genetic dysfunction of androgen receptors, but in male rats, pharmacological stimulation of spinal GRP receptors restores penile reflexes and ejaculation after castration. GRP offers new avenues for understanding potential therapeutic approaches to masculine reproductive dysfunction.

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Figure 1: Origin, targets and androgen dependence of GRP neurons in the lumbar spinal cord.
Figure 2: GRP-Rs in autonomic regions of the lower lumbar spinal cord.
Figure 3: Role of spinal cord GRP system in sexual reflexes.


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We thank A. Takara for technical assistance. Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology, Japan (H.S., K.-I.M. and M.K.) and US National Institutes of Health grant NS28421 (S.M.B.).

Author information

H.S., K.-I.M. and M.K. designed experiments and conducted data analysis. H.S. and H.H. performed histological experiments. H.S. and K.-I.M. performed molecular experiments. H.S. and D.G.Z. performed behavioral experiments. C.L.J., S.M.B., E.W. and K.W. provided Tfm rats, advice, antibodies and equipment. H.S., S.M.B. and M.K. wrote the paper. All authors discussed the results and commented on the manuscript.

Correspondence to Hirotaka Sakamoto.

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Supplementary Figures 1–10, Supplementary Table 1 and Supplementary Methods (PDF 6567 kb)

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Sakamoto, H., Matsuda, K., Zuloaga, D. et al. Sexually dimorphic gastrin releasing peptide system in the spinal cord controls male reproductive functions. Nat Neurosci 11, 634–636 (2008) doi:10.1038/nn.2126

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