Sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord controls masculine reproductive functions in rats

2009 ◽  
Vol 65 ◽  
pp. S41
Author(s):  
Hirotaka Sakamoto ◽  
Ken-Ichi Matsuda ◽  
Damian G. Zuloaga ◽  
Hisayuki Hongu ◽  
Etsuko Wada ◽  
...  
Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 417-421 ◽  
Author(s):  
Hirotaka Sakamoto ◽  
Tatsuo Arii ◽  
Mitsuhiro Kawata

Abstract The spinal nucleus of bulbocavernosus (SNB) is a sexually dimorphic motor nucleus located in the anterior horn of the fifth and sixth lumbar segments of the spinal cord that plays a significant role in male sexual function. We recently found that a sexually dimorphic expression of gastrin-releasing peptide (GRP) in the lumbar spinal cord regulates male copulatory reflexes. Although it is reported that these systems are both profoundly regulated by circulating androgen levels in male rats, no direct evidence has been reported regarding GRP synaptic inputs onto SNB motoneurons. The aim of the current study was to determine the axodendritic synaptic inputs of spinal GRP neurons to SNB motoneurons. Immunoelectron microscopy, combined with a retrograde tracing technique using high-voltage electron microscopy (HVEM), provided a three-dimensional visualization of synaptic contacts from the GRP system in the lumbar spinal cord onto SNB motoneurons. HVEM analysis clearly demonstrated that GRP-immunoreactive axon terminals directly contact dendrites that extend into the dorsal gray commissure from the SNB. These HVEM findings provide an ultrastructural basis for understanding how the spinal GRP system regulates male sexual behavior.


2008 ◽  
Vol 11 (6) ◽  
pp. 634-636 ◽  
Author(s):  
Hirotaka Sakamoto ◽  
Ken-Ichi Matsuda ◽  
Damian G Zuloaga ◽  
Hisayuki Hongu ◽  
Etsuko Wada ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
James W. Wiggins ◽  
Jonathan E. Sledd ◽  
Lique M. Coolen

Spinal cord injury (SCI) in men is commonly associated with sexual dysfunction, including anejaculation, and chronic mid-thoracic contusion injury in male rats also impairs ejaculatory reflexes. Ejaculation is controlled by a spinal ejaculation generator consisting of a population of lumbar spinothalamic (LSt) neurons that control ejaculation through release of four neuropeptides including galanin and gastrin releasing peptide (GRP) onto lumbar and sacral autonomic and motor nuclei. It was recently demonstrated that spinal contusion injury in male rats caused reduction of GRP-immunoreactivity, but not galanin-immunoreactivity in LSt cells, indicative of reduced GRP peptide levels, but inconclusive results for galanin. The current study further tests the hypothesis that contusion injury causes a disruption of GRP and galanin mRNA in LSt cells. Male rats received mid-thoracic contusion injury and galanin and GRP mRNA were visualized 8 weeks later in the lumbar spinal cord using fluorescent in situ hybridization. Spinal cord injury significantly reduced GRP and galanin mRNA in LSt cells. Galanin expression was higher in LSt cells compared to GRP. However, expression of the two transcripts were positively correlated in LSt cells in both sham and SCI animals, suggesting that expression for the two neuropeptides may be co-regulated. Immunofluorescent visualization of galanin and GRP peptides demonstrated a significant reduction in GRP-immunoreactivity, but not galanin in LSt cells, confirming the previous observations. In conclusion, SCI reduced GRP and galanin expression in LSt cells with an apparent greater impact on GRP peptide levels. GRP and galanin are both essential for triggering ejaculation and thus such reduction may contribute to ejaculatory dysfunction following SCI in rats.


Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3672-3679 ◽  
Author(s):  
Hirotaka Sakamoto ◽  
Keiko Takanami ◽  
Damian G. Zuloaga ◽  
Ken-ichi Matsuda ◽  
Cynthia L. Jordan ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document