Prolactin is a fertility hormone produced and released by the anterior pituitary gland. Normal changes in prolactin levels influence fertility and these changes are carefully regulated by neuroendocrine cells in the hypothalamus. Specifically, prolactin surges along with luteinizing hormone to stimulate ovulation and mating behaviors in rodents. Prolactin also follows a twice-daily surge pattern during rodent pregnancy, helping to maintain the pregnancy and prepare the maternal brain for offspring care. Dopamine is the primary regulatory of prolactin and acts through tonic inhibition during non-surge times. High levels of prolactin feedback to stimulate dopamine and thereby reduce prolactin back down to normal, low levels. However, dopamine is not alone in regulating prolactin release. Early mathematical models from the lab helped to identify some shortcomings in the understanding of prolactin regulation. Based on the existing literature, a model was designed to replicate experimental results. When I came to lab and began reviewing this literature and the model's assumptions, I began to ask some important questions: Do dopamine levels change dramatically with the prolactin surges? Does the timing signal in the model really act as an inhibitory signal? Does the stimulatory signal act alone to drive surges of prolactin release? What else is out that that feeds into this circuit? These perfectly timed surges of prolactin must somehow be controlled by the brain's central clock. One clock signal, VIP, has been implicated in indirect prolactin regulation. This neurotransmitter could stimulate prolactin either by inhibiting dopamine or by activating a prolactin simulator. In this dissertation, I show that it may in fact be doing both. Oxytocin is one potential, and particularly potent, prolactin stimulator that is itself implicated in reproduction and the associated social behaviors. Released at the posterior pituitary, I hypothesized that plasma oxytocin levels might be predictive of the large prolactin surges observed during times of fertility and pregnancy. However, the data fail to support such a clear direct correlation. Other hypothalamic factors that have also been proposed to be involved in prolactin regulation include the endogenous opioid dynorphin. One major hypothalamic source of dynorphin are the KNDy neurons that co-secrete kisspeptin, neurokinin B, and dynorphin. All these neurotransmitters have been studied for their roles in luteinizing hormone regulation. Research presented here shows that the KNDy neuron dynorphin, while directly involved in luteinizing hormone surge release, is not involved in prolactin surge release. In fact, another KNDy product is likely involved in the single, estrogen-induced fertility surge, while another, still unknown, source of dynorphin is involved during the twice-daily prolactin surge pattern. Overall, this dissertation explores many aspects beyond just dopamine as possible regulatory inputs to the prolactin control circuit. Our simplified rodent models and the mathematical modeling help to show us the limits of our understanding so we can ask the right questions for the next experiments. This multi-angled approach, employing different physiological states in the animals and discussing possible network scenarios with modelers, gives depth to the research program described in this dissertation. Further work will better elucidate important aspects of fertility regulation that have undoubted implications for human and animal health. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2015. / June 23, 2015. / cervical stimulation, dopamine, dynorphin, estradiol, oxytocin, prolactin / Includes bibliographical references. / Richard Bertram, Professor Co-Directing Dissertation; Paul Trombley, Professor Co-Directing Dissertation; Tim Logan, University Representative; Kim Hughes, Committee Member; Arturo Gonazalez-Iglesias, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_273655 |
| Contributors | Stathopoulos, Andrea Mahi (authoraut), Bertram, R. (Richard) (professor co-directing dissertation), Trombley, Paul Q. (professor co-directing dissertation), Logan, Timothy M., 1961- (university representative), Hughes, Kimberly A., 1960- (committee member), Gonzalez-Iglesias, Arturo Eduardo (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Biological Science (degree granting department) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource (113 pages), computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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