62 Altering sexual behavior of rats through neonatal treatment with an aromatase inhibitor, estrogen receptor antagonist and testosterone

The mammalian brain is sexually dimorphic until becoming imprinted before birth or during neonatal development. The naïve mammalian brain of neonates is programmed to become feminine. In male neonates, testosterone crosses the blood brain barrier where it is converted to estrogen by aromatase. Estrogen in the brain imprints male sexual behavior. In female neonates, estrogen binds to alpha fetoprotein which prohibits estrogen from entering the brain. The present study was undertaken to determine if testosterone, an estrogen receptor antagonist (ICI 182,780) or aromatase inhibitor (Letrozole) would alter sexual behavior in neonatal rats. In this study, the entire litter of neonatal rat pups received a sc injection (100µl) of one of the following four treatments: corn oil (CO), testosterone propionate 100 µg (TP), ICI 182,780 100 µg (ICI), or Letorozole 100 µg (LET) on days 1 and 3 after birth. At approximately 60-70 days of age, treated rats were placed in cages with nontreated rats of the opposite sex. Animals were euthanized after 20 days. Body, testis, epididymal, and accessory gland weights were recorded for males as well as the number of females they bred and litter size. Body weight, pregnancy status, and litter size (if pregnant) were recorded for treated females. While there was a difference (P< 0.001) in body weight between males and females (average 372 g vs 279 g respectively), there was no statistical differences in body, testis, epididymal, or accessory gland weight between male treatment groups. While number of females pregnant or litter size was not different for CO, TP, or ICI, LET males established no pregnancies. Body weight, number pregnant and litter size were not different between female CO, ICI, or LET treatments. However, TP treated females established no pregnancies. Sexual mating behavior is altered by neonatal exposure to an aromatase inhibitor or testosterone in rats.