Many hormones follow seasonal rhythms, but none more so than prolactin. Prolactin is secreted by the pituitary gland at the base of the brain and is high in summer and low in winter. These seasonal changes are driven by the changes in daylight that are transformed into a chemical signal in the body by another hormone, melatonin. Melatonin acts on an enigmatic subdivision of the pituitary gland, the pars tuberalis, to regulate the secretion of an unknown factor that, in turn, drives seasonal prolactin release. In the current project it is hypothesized that the identity of this unknown factor is a "tachykinin". Using sheep as a model, this project will investigate the release of tachykinins by the pars tuberalis and the effect of these tachykinins on prolactin secretion during the different seasons of the year. It is expected that tachykinin production or receptor regulation will differ between seasons and, accordingly, its ability to modulate prolactin release will be seasonally dependent. This research will drive forward an important basic scientific question - establishing what the enigmatic pars tuberalis secretes. This research may also resolve why chromophobic tumors of the pars tuberalis region induce hyperprolactinemia and address the common link between hyperprolactinemia and infertility in mammals. The project will offer unique training opportunities for students who will be expected to present their findings at national and international conferences and these students will have the opportunity to become co-authors on peer-reviewed publications.
All vertebrates exhibit seasonal rhythms in a variety of physiological systems. It is well known that in temperate latitudes most, if not all, of these rhythms are under the direct control of the pineal hormone, melatonin, whose secretion is regulated by daylight. How melatonin controls the rhythmic activity of these systems remains poorly understood. There is compelling evidence from research in sheep that melatonin, acting on a specific subdivision of the pituitary gland, the pars tuberalis, controls the seasonal rhythm in prolactin secretion. Prolactin has numerous functions apart from lactation, including coat growth which may enable the agricultural industry to manipulate coat-growth in sheep and growing commercial concerns such as the alpaca industry. Wool could then be harvested year-round and not just seasonally. It is well known that animals in captivity do not breed well and it is possible that this may be due to hyperprolactinaemia, either seasonal or stress-induced. By understanding the mechanisms underlying prolactin secretion, we it may be possible to eliminate prolactin-induced infertility and could also improve the reproductive health of women. It is also interesting that specific hyperprolactinemia-inducing tumors may occur in the region of the pituitary stalk but these tumors are not classic prolactinomas. Indeed, they have been classified as non-secretory as they are not classical pituitary cells. Understanding what the pars tuberalis secretes may have a profound outcome on the treatment of such tumors. Regulation of prolactin by melatonin is through an unknown factor, hypothetically called tuberalin. The identity of tuberalin is elusive despite an intensive international research effort. We discovered that the pars tuberalis contains an abundance of substance P and neurokinin A-immunoreactive cells and investigated the role of these tachykinins in driving prolactin. We were able to identify individual pars tuberalis cells expressing melatonin receptors for the first time and these overlapped with the tachykinin distribution. However, although we detected substance P in blood flowing from the brain to pituitary gland, this did not change between day and night nor between winter and summer when prolactin levels varied. More directly, we developed a novel method to infuse substances into the pituitary gland of the conscious sheep and found that we could not notably drive prolactin secretion. Whilst conducting these studies, others had reported effects of the thyroid axis on regulating prolactin and infusing thyroid stimulating hormone (TSH) into the pituitary gland did elicit a significant increase in prolactin. In keeping with others, we have not been able to visualize significant numbers of cells in the pars tuberalis that make TSH even though there is a lot of TSH mRNA present. This suggests that TSH is rapidly released, and not stored, and may be the most important tuberalin regulating prolactin
