The central melanocortin receptors have classically been implicated in the maintenance of energy homeostasis, though their expression in hypothalamus and brainstem. Two melanocortin receptors are predominantly expressed in the central nervous system, namely melanocortin -3 and -4 receptors (MC3R and MC4R). While the MC4R has been extensively studied by our lab and others, the function of the MC3R is less well understood. Through the utilization of a mouse model with the MC3R promoter driving green fluorescent protein expression (MC3R-GFP) and another with genetic knockout of the MC3R (MC3R KO), a more extensive study of the function of the MC3R was performed. High expression of the MC3R-GFP was noted in brain regions including the cortex, thalamus, hypothalamus, and ventral midbrain. Following up expression of the MC3R in the ventral tegmental area, MC3R deficiency was shown to alter dopamine homeostasis and sucrose preference in a female specific manner. The alteration in midbrain dopamine content in the MC3R KO female was normalized by ovariectomy. In addition, the response to ovariectomy in the MC3R KO uncovered a significant increase in body weight and body fat in response to surgery in MC3R KO animals. Further studies examining gender-specific control of energy homeostasis were conducted during pregnancy, when ovarian hormone signaling fluctuates. MC3R KO dams showed a deficiency in pregnancy induced food intake and a defect in the accumulation of fat stores in preparation for lactation. However, MC3R KO dams displayed normal body weight gain and food intake response to lactation. These findings demonstrate that the MC3R exerts multiple effects on the regulation of food intake and energy homeostasis that are specific to female animals.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-06172014-112613 |
| Date | 23 June 2014 |
| Creators | Lippert, Rachel Nicole |
| Contributors | Randy Blakely, Ph.D., Danny Winder, Ph.D., Kate Ellacott, Ph.D., Roger Cone, Ph.D., Aurelio Galli, Ph.D., Louis Muglia, M.D., Ph.D., Randy Blakely, Ph.D., Danny Winder, Ph.D., Kate Ellacott, Ph.D., Roger Cone, Ph.D., Aurelio Galli, Ph.D., Louis Muglia, M.D., Ph.D. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-06172014-112613/ |
| Rights | restrictsix, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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