Perinatal testosterone exposure is critical for the development of the male-specific sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that mediates erection and ejaculation

Biology of Sex Differences

Takumi Oti¹  Keiko Takanami¹  Nao Katayama¹  Tomoca Edey¹  Keita Satoh¹  Tatsuya Sakamoto¹  Hirotaka Sakamoto¹ 

[1] Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, 130-17 Kashino, Ushimado, Setouchi 701-4303, Okayama, Japan

关键词: Spinal cord;    Male sexual function;    Gastrin-releasing peptide;    Sexual differentiation;    Androgens;   

Others  :  1235392
DOI  :  10.1186/s13293-016-0058-x

 received in 2015-11-27, accepted in 2016-01-04,  发布年份 2016

【 摘 要 】

Background

In rats, a sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord projects to spinal centers that control erection and ejaculation. This system controls the sexual function of adult males in an androgen-dependent manner. In the present study, we assessed the influence of androgen exposure on the spinal GRP system during a critical period of the development of sexual dimorphism.

Methods

Immunohistochemistry was used to determine if the development of the spinal GRP system is regulated by the perinatal androgen surge. We first analyzed the responses of neonates administered with anti-androgen flutamide. To remove endogenous androgens, rats were castrated at birth. Further, neonatal females were administered androgens during a critical period to evaluate the development of the male-specific spinal GRP system.

Results

Treatment of neonates with flutamide on postnatal days 0 and 1 attenuated the spinal GRP system during adulthood. Castrating male rats at birth resulted in a decrease in the number of GRP neurons and the intensity of neuronal GRP in the spinal cord during adulthood despite testosterone supplementation during puberty. This effect was prevented if the rats were treated with testosterone propionate immediately after castration. Moreover, treating female rats with androgens on the day of birth and the next day, masculinized the spinal GRP system during adulthood, which resembled the masculinized phenotype of adult males and induced a hypermasculine appearance.

Conclusions

The perinatal androgen surge plays a key role in masculinization of the spinal GRP system that controls male sexual behavior. Further, the present study provides potentially new approaches to treat sexual disorders of males.

【 授权许可】

   
2016 Oti et al.

【 图 表 】

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