Cellular Mechanisms of Prolactin Regulation of Oxytocin Neurons in Reproduction
The hormone oxytocin is secreted from nerve terminals of oxytocin magnocellular cells (MNCs) in the posterior pituitary gland and is important in the timing of birth and is essential for milk secretion. Another reproductive hormone, prolactin, is secreted from the anterior pituitary gland and is critical for breast development during pregnancy, as well as for milk synthesis during lactation. Oxytocin MNCs of the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus undergo significant plasticity during pregnancy and lactation. Prolactin receptors are expressed by oxytocin neurons in both of these nuclei and prolactin has been shown to inhibit oxytocin MNCs in virgin rats. This project aimed to test two hypotheses. The first hypothesis was that the inhibitory effects of endogenous prolactin on the electrical activity of oxytocin MNCs will be reduced over the course of pregnancy or early lactation. To test this hypothesis, virgin (dioestrous) and lactating (day 6-12 post-partum) female rats were anaesthetised with urethane and extracellular singleunit recordings were made from identified oxytocin (and vasopressin) MNCs. Prolactin (1 μg in 1 μl intracerebroventricular) reduced the firing rate of oxytocin MNCs in virgin, but not lactating, rats. The second hypothesis was that reproduction-induced adaptations in oxytocin MNC responses to prolactin might be mediated by changes in second messenger systems downstream of the prolactin receptor. Double labelled (for oxytocin and phosphorylated signal transducer and activator of transcription 5 (pSTAT5)) immunohistochemistry was used to examine prolactin-induced activation of the Jak/STAT5 pathway in oxytocin MNCs. pSTAT5 expression was significantly increased in oxytocin MNCs of virgin rats treated with prolactin, while both the vehicle and prolactin treated lactating females had high levels of pSTAT5 in their oxytocin MNCs. Together, these data provide evidence that prolactin may directly and specifically regulates activity of oxytocin MNCs. However, the significance of this regulation remains to be elucidated.
Advisor: Brown, Colin; Grattan, David
Degree Name: Bachelor of Medical Science with Honours
Degree Discipline: Physiology and Anatomy & Structural Biology Departments
Publisher: University of Otago
Keywords: Prolactin; Oxytocin
Research Type: Thesis