Endocrine Abstracts

Among all brain functions, the most strongly sexually differentiated are those which are directly related to reproduction. In addition to neuroendocrine controls of pituitary hormone release, we consider reproductive behaviors whose expression depends on steroid hormones. The hormone-dependent transcriptional activations in hypothalamic neurones long known to be required for female-specific reproductive behaviour, lordosis (Drive, MIT Press, 1999) involve binding to specific DNA response elements by the ligand-activated transcription factor Estrogen Receptor-alpha. Access to these DNA response elements is controlled by structural modifications of the N-termini of histones. I will summarize new data showing estrogen effects on histone chemistry in hypothalamic neurones that regulate lordosis behaviour. With chromatin immunoprecipitation (ChIP) we analyze sites on the promoters of the progesterone receptor and the oxytocin receptor genes, whose associated chromatin is modified by estrogen. As a side point, I will describe surprising relations between estrogenic and thyroid hormone effects on these promoters. In sum, we try to reason from detailed histone modifications in hypothalamic neurons to envision alterations of the defined lordosis behavior circuit, thus to explain the production of a biologically crucial behaviour.