Dave Grattan
Centre for Neuroendocrinology and Department of Anatomy, University of Otago, Dunedin
Prolactin is typically thought of as a hormone required for lactation. Prolactin receptors are expressed throughout the body, however, including pancreas, liver, bone and brain. As such, it is apparent that when prolactin levels are high, such as during pregnancy and lactation, it may exert a wide variety of actions. The well-established role of prolactin in both milk production and maternal behaviour provides a possible insight into why a single hormone might have such pleiotropic actions. We hypothesise that these multiple different actions of prolactin in the body can be considered as one unified function: to promote and coordinate adaptive changes in the mother during pregnancy and lactation to help her cope with the changing physiological demands exerted by these conditions and to facilitate the provision of care and nutrition to dependent offspring. Thus, the same hormonal signals used to stimulate milk production from the mammary gland are also used to coordinate appropriate adaptive responses in the brain and other tissues. Using conditional gene targeting approaches, we are investigating this hypothesis by knocking out prolactin receptor expression in specific tissues, and then evaluating physiological adaptation during pregnancy. For example, specific deletion of prolactin receptors from pancreatic beta cells results in a failure to expand beta-cell numbers during pregnancy, resulting in impaired glucose homeostasis during pregnancy, gestational diabetes, and consequent abnormalities in fetal development. Neuron-specific loss of the prolactin receptor results in increased anxiety, a profound impairment of maternal behaviour and increased neonatal mortality. Thus, it appears that abnormal prolactin signalling during pregnancy, either through reduced levels of prolactin secretion or impaired prolactin signal transduction, might contribute to a range of disorders affecting the pregnancy, with consequences for both mother and infant.