Poster Presentation The International Congress of Neuroendocrinology 2014

Estrogen-induced changes in gene expressions related to the brain sexual differentiation in rodents (#366)

Youki Watanabe 1 , Mototsugu Sakakibara 1 , Yoshihisa Uenoyama 1 , Shiori Minabe 1 , Chikaya Deura 1 , Sho Nakamura 2 , Kei-ichiro Maeda 2 , Hiroko Tsukamura 1
  1. Nagoya University, Nagoya
  2. The University of Tokyo, Tokyo

   The brain mechanism regulating gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge is known to be sexually differentiated in rodents.  Positive estrogen feedback to induce GnRH/LH surge is evident in female rats, whereas male rats never show LH surges, even with a preovulatory level of estradiol (E2). The sexual dimorphism is considered to be due to pre- and/or postnatal sex steroid estrogen converted from testicular androgen.  The purpose of this study is to clarify the mechanisms mediating the estrogen-induced defeminization of LH surge-generating system.

   Female neonatal mice were used for microarray analysis to obtain candidate genes related to sexual differentiation of the brain induced by estrogen.  Female mice were injected with estradiol benzoate (EB) or vehicle on the day of birth, and the hypothalamus was collected at either 1, 3, 6, 12, or 24 h after the EB injection.  More than one hundred genes down-regulated by the EB treatment in a biphasic manner peaked at 3 h and 12-24 h after the EB treatment, while forty to seventy genes were constantly up-regulated after the treatment.  Ptgds, encoding prostaglandin D2 (PGD2) synthase, was chosen for further examination by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the anterior hypothalamus of neonatal male and female rats.

   Ptgds expression was significantly lower in the anterior hypothalamus, but not in the posterior hypothalamus, of male rats than females at the day of birth.  PGD2 have been reported to have a role in neuroprotection, suggesting that Ptgds may be involved in defeminizing the AVPV.  In conclusion, Ptgds could be one of the possible candidate genes, which may mediate the effect of perinatal estrogen involved in sexual differentiation of the LH surge-generating system in rodents.