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Title page for ETD etd-06172014-112613

Type of Document Dissertation
Author Lippert, Rachel Nicole
Author's Email Address rachel.lippert@gmail.com
URN etd-06172014-112613
Title Studies of the Physiological Function of the Melanocortin 3 Receptor
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Danny Winder, Ph.D. Committee Chair
Aurelio Galli, Ph.D. Committee Member
Kate Ellacott, Ph.D. Committee Member
Louis Muglia, M.D., Ph.D. Committee Member
Randy Blakely, Ph.D. Committee Member
Roger Cone, Ph.D. Committee Member
  • food intake
  • reward
  • dopamine
  • ovariectomy
  • pregnancy
  • melanocortin
Date of Defense 2014-05-08
Availability unrestricted
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.
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