Transient neonatal elevation in hypothalamic estrogen receptor mRNA in prenatally-stressed male rats

Abstract

Prenatal stress in rats has been found to alter the sexual dimorphism of brain structures and the sexual behavior of male offspring, pointing to an impaired masculinization of the brain during the perinatal period of brain sexual differentiation. Masculinization of the brain depends on the presence during this critical period of three main elements: adequate levels of testosterone, aromatase activity (locally converting testosterone to estradiol), and brain estrogen receptor (ER) density. In the present study, we measured by reverse transcription-polymerase chain reaction (RT-PCR) the levels of ER messenger RNA (mRNA) expression in the hypothalamus of either prenatally-stressed or control male rats at postnatal (P) days 3, 12 and 90. During the early postnatal period (P3), hypothalamic ER mRNA expression was higher in prenatally stressed male rats (6.12 ± 0.37) than in controls (4.51 ± 0.55) ( P = 0.015). This difference was not, however, found at a later developmental stage (P12, 5.39 ± 0.65 versus 5.39 ± 0.47) or in adult animals (P90, 6.79 ± 1.55 versus 7.07 ± 1.11). This transient elevation of hypothalamic ER mRNA expression resembles the developmental profile of ER mRNA in females. These observations support the idea that androgens play a pivotal role in the demasculinization process, and suggest that testosterone production or aromatization is reduced in prenatally-stressed males during the perinatal period of sexual differentiation, leading to a transient upregulation of unstimulated estrogen receptors.