SAT-410 Kisspeptin is Required for Perinatal Testosterone Surge in Male Rats

Abstract Perinatal testosterone surge derived from testes is critical for masculinization and defeminization of the brain in male rats. Kisspeptin is indispensable for activation of hypothalamus-pituitary-gonadal (HPG) axis to induce testicular testosterone secretion in adult male rats, yet it is unclear if perinatal kisspeptin is responsible for perinatal testosterone surge in male rats. We previously reported that kisspeptin gene knockout (Kiss1-KO) male rats showed high score of lordosis quotient, indicating that kisspeptin is required for defeminization of the brain controlling sexual behaviors. Hence, the present study aimed to investigate the role of kisspeptin in inducing perinatal testosterone surge. First, we examined plasma testosterone and luteinizing hormone (LH) levels at several timepoints during perinatal stage in Kiss1-KO and wild-type (WT) male rats to determine the perinatal testosterone surge and LH elevation. In WT rats, plasma testosterone significantly increased at 0-1.5 and 1.5-3 hours after birth than in embryonic day 21 (E21). Plasma LH also increased significantly at birth (0 hour after birth) than in E21. In contrast, either plasma testosterone or LH was kept at low levels during perinatal period in Kiss1-KO rats. To determine whether external kisspeptin can induce testosterone surge in Kiss1-KO rats, we injected kisspeptin to neonatal males within 2 hours after birth and collected blood samples or brains 1 hour later. After the kisspeptin injection, both plasma testosterone and LH levels were significantly increased in Kiss1-KO rats. Double immunostaining with GnRH and c-Fos revealed that the rate of GnRH neurons expressing c-Fos was significantly higher in Kiss1-KO rats treated with kisspeptin (20.59±4.17%) compared to vehicle-treated Kiss1-KO rats (1.47±1.08%). Taken together, these results suggest that testosterone surge occurring in perinatal male rats, which cause the defeminization of the brain, is kisspeptin dependent and initiation of the testosterone surge is likely to be mediated by kisspeptin-induced activation of HPG axis.