Gene memory in neuroendocrine and behavioural systems.

Area of Science:

• Neuroendocrinology
• Epigenetics
• Molecular Biology

Background:

• Sex steroid hormones induce enduring neuronal alterations in the rat brain, even after hormone levels normalize.
• This phenomenon, termed 'gene memory,' suggests underlying genomic changes.
• Investigating these genomic structural alterations in hypothalamic neurons is crucial.

Purpose of the Study:

• To explore genomic structural alterations in rat hypothalamic neurons responsible for enduring hormone-induced effects.
• To investigate the role of the preproenkephalin gene in oestradiol-mediated neuronal changes and behavior.

Main Methods:

• Analysis of preproenkephalin gene expression and mRNA levels in rat hypothalamus.
• Assessment of tissue-specific and genetic sex-specific regulation of gene expression.
• Examination of DNA methylation patterns in the enkephalin promoter region.

Main Results:

• Oestradiol activates the preproenkephalin gene in a tissue- and sex-specific manner in rat brain neurons.
• Preproenkephalin mRNA levels in the ventromedial hypothalamus correlate with oestradiol-dependent reproductive behavior.
• A tissue-specific DNA methylation pattern was observed in the enkephalin promoter.

Conclusions:

• Oestradiol exposure can lead to enduring epigenetic modifications, such as DNA methylation, in hypothalamic neurons.
• These epigenetic changes in the preproenkephalin gene may underlie 'gene memory' and hormone-influenced behavior.
• Transcription factors interacting with the enkephalin promoter likely play a role in regulating these hormone-induced genomic alterations.