Virtual Presentation SRB Virtual Awards 2020

Kisspeptin reverts hypothyroidism-induced hyperprolactinemia and gonadal hypofunction in male rats (#23)

Luciano Cardoso Santos 1 , Jeane Martinha dos Anjos Cordeiro 2 , Luciana Santos de Oliveira 1 , Erikles Macêdo Barbosa 2 , Larissa da Silva Santana 1 , William Morais Machado 2 , Larissa Rodrigues Santana 2 , Maíra Guimarães Kersul 2 , Patricia Costa Henriques 3 , Roberta Araújo-Lopes 3 , Paola Pereira das Neves Snoeck 2 , Raphael Escorsim Szawka 3 , Juneo Freitas Silva 1
  1. Department of Biological Sciences, State University of Santa Cruz, Ilheus, Bahia, Brazil
  2. Department of Agrarian and Environmental Sciences, State University of Santa Cruz, Ilheus, Bahia, Brazil
  3. Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Hypothyroidism causes infertility in men by suppressing luteinizing hormone release and testicular function. Furthermore, hypothyroidism causes hyperprolactinemia, which is also associated with infertility by reducing the hypothalamic expression of kisspeptin (Kp), the central peptide responsible for gonadotropin-releasing hormone release. In the preset study, we investigated the therapeutic potential of Kp-10 in restoring the suppressive effects of hypothyroidism on the function of the gonadal axis. Hypothyroidism was induced in adult male Wistar rats using 6-propyl-2-thiouracil (4mg/Kg/day) for three months. In the last month, half of the animals received Kp-10 (12 μg/Kg/day). Hypothyroid rats displayed lower testis weight (14%), lower prostate (32%) and seminal vesicle (48%) weight, and reduced plasma levels of LH (21%) and testosterone (62%) compared with control. In addition, hypothyroidism reduced to one third the pituitary levels of Lhβ mRNA, whereas plasma prolactin levels were increased by 4.7-fold (P<0.001). Kp-10 treatment reversed hyperprolactinemia, equaling prolactin to the control levels, and significantly increased plasma LH and testosterone levels, which was associated with recovery of sexual glands weight. Hypothyroidism caused moderate multifocal testicular degeneration and reduced the seminiferous epithelium height, while Kp treatment recovered the number of degenerated tubules and size of the seminiferous epithelium. Hypothyroidism reduced sperm motility and vigor in the thermoresistance testis, altered the integrity of plasma and acrosomal membranes, and increased the number of sperm head defects by 15-fold. The treatment with Kp-10 effectively improved all these sperm parameters (P<0.05), which were fully restored to the control levels in most of the cases. Thus, the present findings reveal that the Kp-10 treatment reverses hyperprolactinemia and improves gonadotropic and testicular function in hypothyroid rats. Our study suggests that kisspeptin analogues may serve as possible alternative therapeutic approach to restore the fertility in hypothyroid men.