Regulation of Progestin Receptor Expression in the Developing Rat Brain by a Dopamine D1 Receptor Antagonist

Abstract

Steroid receptors within the developing brain influence a variety of cellular processes that endure into adulthood, altering both behaviour and physiology. Therefore, it is important to understand how steroid receptor expression is regulated during early brain development. Most studies indicate that oestradiol, by acting upon oestrogen receptors, increases the expression of progestin receptors in the developing brain. We have recently observed an additional mechanism by which dopamine can increase the expression of progestin receptors in developing female rat brain. That is, we found that a dopamine D1 receptor agonist can further increase progestin receptor expression by activating oestrogen receptors in a ligand-independent manner within restricted areas of female brain; however, it is unclear whether dopamine D1 receptors are involved in the normally occurring expression of progestin receptors in developing male and female brain. To investigate this, we examined whether a dopamine D1 receptor antagonist can disrupt the normal developmental expression of progestin receptors in both male and female rat brain. We report that treatment with a dopamine D1 receptor antagonist reduces progestin receptor expression within some, but not all, regions of the developing rat brain in a sex-specific manner. Some of the current findings also suggest that dopamine might be acting to prevent sex differences in progestin receptor expression in some areas while contributing to a sex difference in other areas.