Sex steroids and fos expression in the CNS of prepubertal and newborn rats

Abstract

Fos-like immunoreactivity (IR) within estrogen-concentrating regions of the hypothalamus and within sexually dimorphic regions of the hypothalamus and spinal cord was studied both as a function of estrogen treatment and during specific stages of postnatal development. Two sets of experiments were performed. First, Fos expression in the arcuate (Arc) and ventromedial (VMN) nuclei of the hypothalamus of 25-day-old female rats was examined 1, 3, and 6 h after estrogen treatment. Since (1) estrogen has been shown to stimulate synapse formation in the Arc of 25-day-old female rats, and (2) the Arc and VMN express among the highest levels of estrogen receptor in brain, we hypothesized that estrogen treatment might lead to a rapid induction of Fos-like IR in these areas. Second, Fos expression in the brain and spinal cord of newborn and 10-day-old male and female rats was examined and compared. Particular attention was given to specific sexually dimorphic nuclei of the hypothalamus and spinal cord and to regions of the mediobasal hypothalamus known to contain high levels of gonadal steroid receptors. Since many studies have shown that neuronal development within sexually dimorphic areas of the hypothalamus and spinal cord is influenced by gonadal steroids around the time of birth, we hypothesized that Fos expression within such areas might differ between males and females at birth. We report that, in spite of the well-documented effects of gonadal steroids on the development and function of these areas, no effects of estrogen on Fos expression in the Arc or VMN of the 25-day-old animals and no difference in Fos expression between male and female newborn or 10-day-old animals were observed. In the 25-day-old animals, cell counts revealed an increase in the number of Fos-like IR cells in the VMN and Arc 1 and 3 h after estrogen treatment; however, a comparable effect was observed after treatment with vehicle, suggesting that the induction observed did not reflect an effect of estrogen per se, but may have been due to the stress associated with receiving an injection. A similar induction of Fos-like IR cells within the parvocellular region of the paraventricular nucleus of the hypothalamus was observed following injections of either estrogen or vehicle. In newborn and 10-day-old animals, very few Fos-like IR cells in the medial preoptic area, VMN, and Are of the hypothalamus were observed. In addition, no Fos-like IR motor neurons were observed in the spinal nucleus of the bulbocavernosus nor in the dorsolateral nucleus of the spinal cord. Consequently, no evidence to suggest a relationship between Fos expression and the effects of perinatal exposure to gonadal steroids on the postnatal development of these areas was obtained. The results, however, point to other areas of the brain in which Fos expression may play an important role during postnatal development. In particular, many Fos-like IR cells were observed in the striatum, neocortex, pyriform cortex, endopyriform nucleus, paraventricular nucleus of the thalamus, and the hippocampal formation, as well as within specific hypothalamic nuclei including the paraventricular, supraoptic, and suprachiasmatic nuclei. Specific patterns of staining were observed, some of which were different by 10 days after birth. Most striking was the striatum in which Fos-like IR cells were distributed in patches and along the border adjacent to the corpus callosum on Postnatal Day 0, but were no longer observed 10 days after birth. These data were confirmed by in situ hybridization studies in which the expression and distribution of c-fos mRNA in many of these areas were consistent with the distribution of Fos-like IR cells.