Critical role of androgen receptor in the postnatal period in male sexual behavior in rats.
Gonadal hormones have a developmental role in organization of the nervous system that regulates sexually dimorphic behavior. It is well known that androgen secreted from testes in the perinatal period is converted to estrogen by aromatase in rodent brain, and that estrogen and its receptor play a pivotal role in masculinization of brain structure and function. Treatment with flutamide, an androgen receptor (AR) antagonist, during the perinatal period inhibits development of malespecific brain structure and function, suggesting that androgen signaling via AR also influences brain masculinization. In this study, we investigated which stage during the postnatal period is critical for androgen signaling in brain masculinization. The postnatal period was designated as postnatal days (PD) 0-22, and divided into stages I (PD 0-7), II (PD 8-14), and III (PD 15-22). Newborn male rats were given flutamide subcutaneously in each stage. After adulthood, the effects of postnatal flutamide treatment on brain masculinization were evaluated byanalysis of male sexual behavior. Continuous inhibition of AR throughout stages I and II caused a robust reduction of the intromission ratio and ejaculation frequency compared with other groups. AR inhibition in stage I, II, or III did not cause any change. AR inhibition had no effect onmount behavior. These results show that stage-specific AR activation in the first two postnatal weeks may contribute to brain masculinization mediating male sexual behavior in adulthood.
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shunji
S
Yamada
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Miku
M
Ohoya
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Keiko
K
Takanami
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: matsuken@koto.kpu-m.ac.jp.
Ken Ichi
KI
Matsuda
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mitsuhiro
M
Kawata
D000367:Age Factors; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D004542:Ejaculation / Q000187:drug effects; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D015398:Signal Transduction
D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen; D005485:Flutamide
Androgen receptor; Flutamide; Male sexual behavior; Masculinization; Postnatal period