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Published on: May 12, 2015
Sex differences in oestrogen-induced p44/42 MAPK phosphorylation in the mouse brain in vivo
K Barabás1, E M Szegõ, A Kaszás
1Neurobiology Research Group of Hungarian Academy of Sciences at Eötvös Loránd University, Budapest, Hungary.
Abstract:
In addition to the classical direct genomic mechanisms of action, oestrogen also exerts poorly understood, nonclassical effects on the signalling system in neurones. In the present study, we investigated whether sex differences exist in gonadectomy- and oestrogen-induced effects on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in specific brain regions of mice. We demonstrate that MAPK immunoreactivity was not altered by gonadectomy or oestrogen treatment in either sex. However, we show that the level of phosphorylated MAPK (pMAPK) within the anteroventral periventricular nucleus (AVPV) was consistently higher in males than females irrespective of gonadal steroid hormone status. In addition, gonadectomy was found to decrease pMAPK immunoreactivity within the piriform cortex of males. Oestrogen increased pMAPK immunoreactivity in the medial preoptic area and AVPV of females, but failed to have the same effect in male mice. Overall, these results demonstrate a marked sex difference in oestrogen-induced alteration of MAPK phosphorylation in the brain in vivo.
Insights
Estrogen affects brain signaling differently in male and female mice. Oestrogen (estrogen) increased phosphorylated MAPK (pMAPK) in females but not males, revealing significant sex differences in brain responses.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Estrogen exerts nonclassical effects on neuronal signaling beyond genomic mechanisms.
- Understanding these nonclassical effects, particularly sex differences, is crucial for neuroscience research.
Purpose of the Study:
- To investigate sex differences in gonadectomy- and estrogen-induced effects on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in specific mouse brain regions.
- To elucidate the role of gonadal steroid hormones in modulating MAPK phosphorylation in a sex-specific manner.
Main Methods:
- Utilized immunohistochemistry to assess MAPK and phosphorylated MAPK (pMAPK) levels in specific brain regions of male and female mice.
- Administered gonadectomy and estrogen treatments to manipulate gonadal steroid hormone status.
- Compared pMAPK levels across different treatment groups and sexes.
Main Results:
- No significant changes in overall MAPK immunoreactivity were observed following gonadectomy or estrogen treatment in either sex.
- Consistently higher pMAPK levels were found in the anteroventral periventricular nucleus (AVPV) of males compared to females, irrespective of gonadal status.
- Gonadectomy decreased pMAPK in the piriform cortex of males, while estrogen increased pMAPK in the medial preoptic area and AVPV of females, with no comparable effect in males.
Conclusions:
- Demonstrated a marked sex difference in estrogen-induced alterations of MAPK phosphorylation in the mouse brain in vivo.
- Suggests distinct pathways mediating estrogen's nonclassical effects on neuronal signaling between sexes.
- Highlights the importance of considering sex as a biological variable in neuroendocrine research.

