Hormone receptors in the brain

Abstract

Reproductive behaviours are regulated by gonadal steroids. In most mammalian species sexual activities decline or disappear following gonadectomy and can be reinstated by administering exogenous steroids systemically or by direct application to the brain. It is generally believed that the gonadal hormones act in the brain as they do in peripheral target tissues by binding selectively to cytoplasmic protein ‘receptors’ with subsequent translocation of the hormone-receptor complex to the nuclear chromatin material. Chromatin binding is thought to induce genomic activation, RNA and protein synthesis and, thereby, the regulation of cell function.

Evidence is presented here that indicates that chromatin binding of oestradiol in hypothalamic cells is correlated with the potential to display sexual behaviour. For example, female rats which display receptive behaviour when given oestradiol bind more oestradiol in hypothalamic chromatin than do male rats which are relatively insensitive to oestradiol.

The role of cytoplasmic oestradiol receptors in hormone action is also discussed. The hypothesis is advanced that oestradiol regulates the molecular configuration of the receptor in a dose-dependent fashion and that receptor configuration determines chromatin acceptor site binding and functional activity. Kinetic data are presented which indicate that hypothalamic receptors change their characteristics as a function of hormone dose.