Brain Estrogens and Feeding Behavior

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1043)

Abstract

Estrogens play essential roles in suppressing food intake and preventing body weight gain. Tremendous research efforts have been focused on estrogen physiology in the context of feeding control. Estrogen receptors and the related signals have been attractive targets for development of new obesity therapies. This chapter focuses on the functional interactions between brain estrogens and other appetite-regulatory signals, the critical estrogen receptor isoforms and distinct brain regions that mediate effects of estrogens on feeding, and the intracellular signals that are involved.

References

  1. Alexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J. A., Nonneman, R. J., Hartmann, J., Moy, S. S., Nicolelis, M. A., et al. (2009). Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron, 63, 27–39.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Alingh Prins, A., de Jong-Nagelsmit, A., Keijser, J., & Strubbe, J. H. (1986). Daily rhythms of feeding in the genetically obese and lean Zucker rats. Physiology & Behavior, 38, 423–426.CrossRefGoogle Scholar
  3. Allende-Vigo, M. Z. (2008). Women and the metabolic syndrome: An overview of its peculiarities. Puerto Rico Health Sciences Journal, 27, 190–195.PubMedGoogle Scholar
  4. Aponte, Y., Atasoy, D., & Sternson, S. M. (2011). AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nature Neuroscience, 14, 351–355.CrossRefPubMedGoogle Scholar
  5. Arnold, M., Mura, A., Langhans, W., & Geary, N. (2006). Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat. The Journal of Neuroscience, 26, 11052–11060.CrossRefPubMedGoogle Scholar
  6. Asarian, L., & Geary, N. (1999). Cyclic estradiol treatment phasically potentiates endogenous cholecystokinin’s satiating action in ovariectomized rats. Peptides, 20, 445–450.CrossRefPubMedGoogle Scholar
  7. Asarian, L., & Geary, N. (2007). Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology, 148, 5656–5666.CrossRefPubMedGoogle Scholar
  8. Bailer, U. F., Frank, G. K., Henry, S. E., Price, J. C., Meltzer, C. C., Becker, C., Ziolko, S. K., Mathis, C. A., Wagner, A., Barbarich-Marsteller, N. C., et al. (2007). Serotonin transporter binding after recovery from eating disorders. Psychopharmacology, 195, 315–324.CrossRefPubMedGoogle Scholar
  9. Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Jr., Elmquist, J. K., et al. (2004). Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron, 42, 983–991.CrossRefPubMedGoogle Scholar
  10. Berglund, E. D., Liu, C., Sohn, J. W., Liu, T., Kim, M. H., Lee, C. E., Vianna, C. R., Williams, K. W., Xu, Y., & Elmquist, J. K. (2013). Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. The Journal of Clinical Investigation, 123, 5061–5070.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bewick, G. A., Gardiner, J. V., Dhillo, W. S., Kent, A. S., White, N. E., Webster, Z., Ghatei, M. A., & Bloom, S. R. (2005). Post-embryonic ablation of AgRP neurons in mice leads to a lean, hypophagic phenotype. The FASEB Journal, 19, 1680–1682.CrossRefPubMedGoogle Scholar
  12. Billeci, A. M., Paciaroni, M., Caso, V., & Agnelli, G. (2008). Hormone replacement therapy and stroke. Current Vascular Pharmacology, 6, 112–123.CrossRefPubMedGoogle Scholar
  13. Blaustein, J. D., & Wade, G. N. (1976). Ovarian influences on the meal patterns of female rats. Physiology & Behavior, 17, 201–208.CrossRefGoogle Scholar
  14. Blundell, J. E., & Leshem, M. B. (1974). Central action of anorexic agents: Effects of amphetamine and fenfluramine in rats with lateral hypothalamic lesions. European Journal of Pharmacology, 28, 81–88.CrossRefPubMedGoogle Scholar
  15. Bruning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Muller-Wieland, D., & Kahn, C. R. (2000). Role of brain insulin receptor in control of body weight and reproduction. Science, 289, 2122–2125.CrossRefPubMedGoogle Scholar
  16. Butera, P. C., & Beikirch, R. J. (1989). Central implants of diluted estradiol: Independent effects on ingestive and reproductive behaviors of ovariectomized rats. Brain Research, 491, 266–273.CrossRefPubMedGoogle Scholar
  17. Butera, P. C., Willard, D. M., & Raymond, S. A. (1992). Effects of PVN lesions on the responsiveness of female rats to estradiol. Brain Research, 576, 304–310.CrossRefPubMedGoogle Scholar
  18. Butera, P. C., Bradway, D. M., & Cataldo, N. J. (1993). Modulation of the satiety effect of cholecystokinin by estradiol. Physiology & Behavior, 53, 1235–1238.CrossRefGoogle Scholar
  19. Callewaert, F., Venken, K., Ophoff, J., De Gendt, K., Torcasio, A., van Lenthe, G. H., Van Oosterwyck, H., Boonen, S., Bouillon, R., Verhoeven, G., et al. (2009). Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha. The FASEB Journal, 23, 232–240.CrossRefPubMedGoogle Scholar
  20. Cao, X., Xu, P., Oyola, M. G., Xia, Y., Yan, X., Saito, K., Zou, F., Wang, C., Yang, Y., Hinton, A., Jr., et al. (2014). Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. The Journal of Clinical Investigation, 124, 4351–4362.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Challis, B. G., Pritchard, L. E., Creemers, J. W., Delplanque, J., Keogh, J. M., Luan, J., Wareham, N. J., Yeo, G. S., Bhattacharyya, S., Froguel, P., et al. (2002). A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Human Molecular Genetics, 11, 1997–2004.Google Scholar
  22. Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006). Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes, 55, 978–987.CrossRefPubMedGoogle Scholar
  23. Clegg, D. J., Brown, L. M., Zigman, J. M., Kemp, C. J., Strader, A. D., Benoit, S. C., Woods, S. C., Mangiaracina, M., & Geary, N. (2007). Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes, 56, 1051–1058.CrossRefPubMedGoogle Scholar
  24. Cone, R. D. (1999). The central melanocortin system and energy homeostasis. Trends in Endocrinology and Metabolism, 10, 211–216.CrossRefPubMedGoogle Scholar
  25. Cone, R. D. (2005). Anatomy and regulation of the central melanocortin system. Nature Neuroscience, 8, 571–578.CrossRefPubMedGoogle Scholar
  26. Creemers, J. W., Lee, Y. S., Oliver, R. L., Bahceci, M., Tuzcu, A., Gokalp, D., Keogh, J., Herber, S., White, A., O'Rahilly, S., et al. (2008). Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway. The Journal of Clinical Endocrinology and Metabolism, 93, 4494–4499.CrossRefPubMedGoogle Scholar
  27. Dalmasso, C., Amigone, J. L., & Vivas, L. (2011). Serotonergic system involvement in the inhibitory action of estrogen on induced sodium appetite in female rats. Physiology & Behavior, 104, 398–407.CrossRefGoogle Scholar
  28. Dauncey, M. J. (1986). Activity-induced thermogenesis in lean and genetically obese (ob/ob) mice. Experientia, 42, 547–549.CrossRefPubMedGoogle Scholar
  29. Dauncey, M. J., & Brown, D. (1987). Role of activity-induced thermogenesis in twenty-four hour energy expenditure of lean and genetically obese (ob/ob) mice. Quarterly Journal of Experimental Physiology, 72, 549–559.CrossRefPubMedGoogle Scholar
  30. Davidson, T. L., Kanoski, S. E., Tracy, A. L., Walls, E. K., Clegg, D., & Benoit, S. C. (2005). The interoceptive cue properties of ghrelin generalize to cues produced by food deprivation. Peptides, 26, 1602–1610.CrossRefPubMedGoogle Scholar
  31. Davis, K. E., Carstens, E. J., Irani, B. G., Gent, L. M., Hahner, L. M., & Clegg, D. J. (2014). Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. Hormones and Behavior, 66, 196–207.CrossRefPubMedPubMedCentralGoogle Scholar
  32. De Fanti, B. A., Hamilton, J. S., & Horwitz, B. A. (2001). Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats. Brain Research, 902, 164–170.CrossRefPubMedGoogle Scholar
  33. de Souza, F. S., Nasif, S., Lopez-Leal, R., Levi, D. H., Low, M. J., & Rubinsten, M. (2011). The estrogen receptor alpha colocalizes with proopiomelanocortin in hypothalamic neurons and binds to a conserved motif present in the neuron-specific enhancer nPE2. European Journal of Pharmacology, 660, 181–187.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Diano, S., Kalra, S. P., Sakamoto, H., & Horvath, T. L. (1998). Leptin receptors in estrogen receptor-containing neurons of the female rat hypothalamus. Brain Research, 812, 256–259.CrossRefPubMedGoogle Scholar
  35. DiNardo, L. A., & Travers, J. B. (1997). Distribution of fos-like immunoreactivity in the medullary reticular formation of the rat after gustatory elicited ingestion and rejection behaviors. The Journal of Neuroscience, 17, 3826–3839.PubMedGoogle Scholar
  36. Drewett, R. F. (1973). Sexual behaviour and sexual motivation in the female rat. Nature, 242, 476–477.CrossRefPubMedGoogle Scholar
  37. Eckel, L. A., & Geary, N. (1999). Endogenous cholecystokinin’s satiating action increases during estrus in female rats. Peptides, 20, 451–456.CrossRefPubMedGoogle Scholar
  38. Eckel, L. A., & Geary, N. (2001). Estradiol treatment increases feeding-induced c-Fos expression in the brains of ovariectomized rats. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 281, R738–R746.CrossRefPubMedGoogle Scholar
  39. Eckel, L. A., Houpt, T. A., & Geary, N. (2002). Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 283, R1378–R1385.CrossRefPubMedGoogle Scholar
  40. Elmquist, J. K., Elias, C. F., & Saper, C. B. (1999). From lesions to leptin: Hypothalamic control of food intake and body weight. Neuron, 22, 221–232.CrossRefPubMedGoogle Scholar
  41. Farooqi, I. S., Drop, S., Clements, A., Keogh, J. M., Biernacka, J., Lowenbein, S., Challis, B. G., & O'Rahilly, S. (2006). Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes, 55, 2549–2553.CrossRefPubMedGoogle Scholar
  42. Feng, Y., Manka, D., Wagner, K. U., & Khan, S. A. (2007). Estrogen receptor-alpha expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice. Proceedings of the National Academy of Sciences of the United States of America, 104, 14718–14723.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Ferguson, S. M., Eskenazi, D., Ishikawa, M., Wanat, M. J., Phillips, P. E., Dong, Y., Roth, B. L., & Neumaier, J. F. (2011). Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization. Nature Neuroscience, 14, 22–24.CrossRefPubMedGoogle Scholar
  44. Finan, B., Yang, B., Ottaway, N., Stemmer, K., Muller, T. D., Yi, C. X., Habegger, K., Schriever, S. C., Garcia-Caceres, C., Kabra, D. G., et al. (2012). Targeted estrogen delivery reverses the metabolic syndrome. Nature Medicine, 18, 1847–1856.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Foltin, R. W., & Moran, T. H. (1989). Food intake in baboons: effects of a long-acting cholecystokinin analog. Appetite, 12, 145–152.CrossRefPubMedGoogle Scholar
  46. Foryst-Ludwig, A., Clemenz, M., Hohmann, S., Hartge, M., Sprang, C., Frost, N., Krikov, M., Bhanot, S., Barros, R., Morani, A., et al. (2008). Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma. PLoS Genetics, 4, e1000108.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C. S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C. A., Roberts, J. L., et al. (2007). Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine, 13, 89–94.CrossRefPubMedGoogle Scholar
  48. Geary, N., Smith, G. P., & Corp, E. S. (1996). The increased satiating potency of CCK-8 by estradiol is not mediated by upregulation of NTS CCK receptors. Brain Research, 719, 179–186.CrossRefPubMedGoogle Scholar
  49. Geary, N., Asarian, L., Korach, K. S., Pfaff, D. W., & Ogawa, S. (2001). Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice. Endocrinology, 142, 4751–4757.CrossRefPubMedGoogle Scholar
  50. Geyer, M. A., Puerto, A., Menkes, D. B., Segal, D. S., & Mandell, A. J. (1976). Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. Brain Research, 106, 257–269.CrossRefPubMedGoogle Scholar
  51. Ghosh, M. N., & Parvathy, S. (1973). The effect of cyproheptadine on water and food intake and on body weight in the fasted adult and weanling rats. British Journal of Pharmacology, 48, 328P–329P.PubMedPubMedCentralGoogle Scholar
  52. Gropp, E., Shanabrough, M., Borok, E., Xu, A. W., Janoschek, R., Buch, T., Plum, L., Balthasar, N., Hampel, B., Waisman, A., et al. (2005). Agouti-related peptide-expressing neurons are mandatory for feeding. Nature Neuroscience, 8, 1289–1291.CrossRefPubMedGoogle Scholar
  53. Grumbach, M. M., & Auchus, R. J. (1999). Estrogen: consequences and implications of human mutations in synthesis and action. The Journal of Clinical Endocrinology and Metabolism, 84, 4677–4694.PubMedGoogle Scholar
  54. Haas, E., Bhattacharya, I., Brailoiu, E., Damjanovic, M., Brailoiu, G. C., Gao, X., Mueller-Guerre, L., Marjon, N. A., Gut, A., Minotti, R., et al. (2009). Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity. Circulation Research, 104, 288–291.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997). Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proceedings of the National Academy of Sciences of the United States of America, 94, 8878–8883.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Handgraaf, S., Riant, E., Fabre, A., Waget, A., Burcelin, R., Liere, P., Krust, A., Chambon, P., Arnal, J. F., & Gourdy, P. (2013). Prevention of obesity and insulin resistance by estrogens requires ERalpha activation function-2 (ERalphaAF-2), whereas ERalphaAF-1 is dispensable. Diabetes, 62, 4098–4108.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000). Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 97, 12729–12734.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Hirosawa, M., Minata, M., Harada, K. H., Hitomi, T., Krust, A., & Koizumi, A. (2008). Ablation of estrogen receptor alpha (ERalpha) prevents upregulation of POMC by leptin and insulin. Biochemical and Biophysical Research Communications, 371, 320–323.CrossRefPubMedGoogle Scholar
  59. Hrupka, B. J., Smith, G. P., & Geary, N. (2002). Hypothalamic implants of dilute estradiol fail to reduce feeding in ovariectomized rats. Physiology & Behavior, 77, 233–241.CrossRefGoogle Scholar
  60. Huang, Y. S., Doi, R., Chowdhury, P., Pasley, J. N., Nishikawa, M., Huang, T. J., & Rayford, P. L. (1993). Effect of cholecystokinin on food intake at different stages of the estrous cycle in female rats. Journal of the Association for Academic Minority Physicians, 4, 56–58.PubMedGoogle Scholar
  61. Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88, 131–141.CrossRefPubMedGoogle Scholar
  62. Jakacka, M., Ito, M., Martinson, F., Ishikawa, T., Lee, E. J., & Jameson, J. L. (2002). An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. Molecular Endocrinology, 16, 2188–2201.CrossRefPubMedGoogle Scholar
  63. Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., et al. (2000). Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proceedings of the National Academy of Sciences of the United States of America, 97, 12735–12740.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Kim, J. H., Meyers, M. S., Khuder, S. S., Abdallah, S. L., Muturi, H. T., Russo, L., Tate, C. R., Hevener, A. L., Najjar, S. M., Leloup, C., et al. (2014). Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. Molecular Metabolism, 3, 177–190.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Koch, M., Varela, L., Kim, J. G., Kim, J. D., Hernandez-Nuno, F., Simonds, S. E., Castorena, C. M., Vianna, C. R., Elmquist, J. K., Morozov, Y. M., et al. (2015). Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature, 519, 45–50.CrossRefPubMedPubMedCentralGoogle Scholar
  66. Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011). Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. The Journal of Clinical Investigation, 121(4), 1424–1428.CrossRefPubMedPubMedCentralGoogle Scholar
  67. Lechin, F., van der Dijs, B., & Hernandez-Adrian, G. (2006). Dorsal raphe vs. median raphe serotonergic antagonism. Anatomical, physiological, behavioral, neuroendocrinological, neuropharmacological and clinical evidences: relevance for neuropharmacological therapy. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 30, 565–585.CrossRefGoogle Scholar
  68. Leibel, R. L., Chung, W. K., & Chua, S. C., Jr. (1997). The molecular genetics of rodent single gene obesities. The Journal of Biological Chemistry, 272, 31937–31940.CrossRefPubMedGoogle Scholar
  69. Li, B. H., & Rowland, N. E. (1994). Cholecystokinin- and dexfenfluramine-induced anorexia compared using devazepide and c-fos expression in the rat brain. Regulatory Peptides, 50, 223–233.CrossRefPubMedGoogle Scholar
  70. Lindell, K., Bennett, P. A., Itoh, Y., Robinson, I. C., Carlsson, L. M., & Carlsson, B. (2001). Leptin receptor 5'untranslated regions in the rat: relative abundance, genomic organization and relation to putative response elements. Molecular and Cellular Endocrinology, 172, 37–45.CrossRefPubMedGoogle Scholar
  71. Liu, S., Le May, C., Wong, W. P., Ward, R. D., Clegg, D. J., Marcelli, M., Korach, K. S., & Mauvais-Jarvis, F. (2009). Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes, 58, 2292–2302.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Malyala, A., Zhang, C., Bryant, D. N., Kelly, M. J., & Ronnekleiv, O. K. (2008). PI3K signaling effects in hypothalamic neurons mediated by estrogen. The Journal of Comparative Neurology, 506, 895–911.CrossRefPubMedGoogle Scholar
  73. Martensson, U. E., Salehi, S. A., Windahl, S., Gomez, M. F., Sward, K., Daszkiewicz-Nilsson, J., Wendt, A., Andersson, N., Hellstrand, P., Grande, P. O., et al. (2009). Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice. Endocrinology, 150, 687–698.CrossRefPubMedGoogle Scholar
  74. Mauvais-Jarvis, F., Manson, J. E., Stevenson, J. C., & Fonseca, V. A. (2017). Menopausal hormone therapy and type 2 diabetes prevention: Evidence, mechanisms, and clinical implications. Endocrine Reviews, 38, 173–188.CrossRefPubMedGoogle Scholar
  75. McGuirk, J., Goodall, E., Silverstone, T., & Willner, P. (1991). Differential effects of d-fenfluramine, l-fenfluramine and d-amphetamine on the microstructure of human eating behaviour. Behavioural Pharmacology, 2, 113–119.CrossRefPubMedGoogle Scholar
  76. McLaughlin, C. L., & Baile, C. A. (1981). Ontogeny of feeding behavior in the Zucker obese rat. Physiology & Behavior, 26, 607–612.CrossRefGoogle Scholar
  77. Merchenthaler, I., Lane, M. V., Numan, S., & Dellovade, T. L. (2004). Distribution of estrogen receptor alpha and beta in the mouse central nervous system: in vivo autoradiographic and immunocytochemical analyses. The Journal of Comparative Neurology, 473, 270–291.CrossRefPubMedGoogle Scholar
  78. Miller, M. M., Tousignant, P., Yang, U., Pedvis, S., & Billiar, R. B. (1995). Effects of age and long-term ovariectomy on the estrogen-receptor containing subpopulations of beta-endorphin-immunoreactive neurons in the arcuate nucleus of female C57BL/6J mice. Neuroendocrinology, 61, 542–551.CrossRefPubMedGoogle Scholar
  79. Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006). Central nervous system control of food intake and body weight. Nature, 443, 289–295.CrossRefPubMedGoogle Scholar
  80. Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., & Matsukura, S. (2001). A role for ghrelin in the central regulation of feeding. Nature, 409, 194–198.CrossRefPubMedGoogle Scholar
  81. Ohlsson, C., Hellberg, N., Parini, P., Vidal, O., Bohlooly, Y. M., Rudling, M., Lindberg, M. K., Warner, M., Angelin, B., & Gustafsson, J. A. (2000). Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochemical and Biophysical Research Communications, 278, 640–645.CrossRefPubMedGoogle Scholar
  82. Okura, T., Koda, M., Ando, F., Niino, N., Ohta, S., & Shimokata, H. (2003). Association of polymorphisms in the estrogen receptor alpha gene with body fat distribution. International Journal of Obesity and Related Metabolic Disorders, 27, 1020–1027.CrossRefPubMedGoogle Scholar
  83. Olofsson, L. E., Pierce, A. A., & Xu, A. W. (2009). Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake. Proceedings of the National Academy of Sciences of the United States of America, 106, 15932–15937.CrossRefPubMedPubMedCentralGoogle Scholar
  84. Osterlund, M., Kuiper, G. G., Gustafsson, J. A., & Hurd, Y. L. (1998). Differential distribution and regulation of estrogen receptor-alpha and -beta mRNA within the female rat brain. Brain Research Molecular Brain Research, 54, 175–180.CrossRefPubMedGoogle Scholar
  85. Otto, C., Fuchs, I., Kauselmann, G., Kern, H., Zevnik, B., Andreasen, P., Schwarz, G., Altmann, H., Klewer, M., Schoor, M., et al. (2009). GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biology of Reproduction, 80, 34–41.CrossRefPubMedGoogle Scholar
  86. Paez, X., & Myers, R. D. (1991). Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus. Peptides, 12, 609–616.CrossRefPubMedGoogle Scholar
  87. Palmer, K., & Gray, J. M. (1986). Central vs. peripheral effects of estrogen on food intake and lipoprotein lipase activity in ovariectomized rats. Physiology & Behavior, 37, 187–189.CrossRefGoogle Scholar
  88. Park, T. H., & Carr, K. D. (1998). Neuroanatomical patterns of fos-like immunoreactivity induced by a palatable meal and meal-paired environment in saline- and naltrexone-treated rats. Brain Research, 805, 169–180.CrossRefPubMedGoogle Scholar
  89. Park, C. J., Zhao, Z., Glidewell-Kenney, C., Lazic, M., Chambon, P., Krust, A., Weiss, J., Clegg, D. J., Dunaif, A., Jameson, J. L., et al. (2011). Genetic rescue of nonclassical ERalpha signaling normalizes energy balance in obese Eralpha-null mutant mice. The Journal of Clinical Investigation, 121, 604–612.CrossRefPubMedPubMedCentralGoogle Scholar
  90. Pedram, A., Razandi, M., Kim, J. K., O'Mahony, F., Lee, E. Y., Luderer, U., & Levin, E. R. (2008). Developmental phenotype of a membrane only estrogen receptor alpha (MOER) mouse. The Journal of Biological Chemistry, 284(6), 3488–3495.CrossRefPubMedGoogle Scholar
  91. Pelletier, G., Li, S., Luu-The, V., & Labrie, F. (2007). Oestrogenic regulation of pro-opiomelanocortin, neuropeptide Y and corticotrophin-releasing hormone mRNAs in mouse hypothalamus. Journal of Neuroendocrinology, 19, 426–431.CrossRefPubMedGoogle Scholar
  92. Pierroz, D. D., Catzeflis, C., Aebi, A. C., Rivier, J. E., & Aubert, M. L. (1996). Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats. Endocrinology, 137, 3–12.CrossRefPubMedGoogle Scholar
  93. Qian, S., Chen, H., Weingarth, D., Trumbauer, M. E., Novi, D. E., Guan, X., Yu, H., Shen, Z., Feng, Y., Frazier, E., et al. (2002). Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Molecular and Cellular Biology, 22, 5027–5035.CrossRefPubMedPubMedCentralGoogle Scholar
  94. Qiu, J., Bosch, M. A., Tobias, S. C., Grandy, D. K., Scanlan, T. S., Ronnekleiv, O. K., & Kelly, M. J. (2003). Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C. The Journal of Neuroscience, 23, 9529–9540.PubMedGoogle Scholar
  95. Raybould, H. E. (2007). Mechanisms of CCK signaling from gut to brain. Current Opinion in Pharmacology, 7, 570–574.CrossRefPubMedPubMedCentralGoogle Scholar
  96. Rinaman, L., Hoffman, G. E., Dohanics, J., Le, W. W., Stricker, E. M., & Verbalis, J. G. (1995). Cholecystokinin activates catecholaminergic neurons in the caudal medulla that innervate the paraventricular nucleus of the hypothalamus in rats. The Journal of Comparative Neurology, 360, 246–256.CrossRefPubMedGoogle Scholar
  97. Rinaman, L., Baker, E. A., Hoffman, G. E., Stricker, E. M., & Verbalis, J. G. (1998). Medullary c-Fos activation in rats after ingestion of a satiating meal. The American Journal of Physiology, 275, R262–R268.PubMedGoogle Scholar
  98. Rivera, H. M., Oberbeck, D. R., Kwon, B., Houpt, T. A., & Eckel, L. A. (2009). Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats. Brain Research, 1259, 51–58.CrossRefPubMedPubMedCentralGoogle Scholar
  99. Rivera, H. M., Santollo, J., Nikonova, L. V., & Eckel, L. A. (2012). Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. Physiology & Behavior, 105, 188–194.CrossRefGoogle Scholar
  100. Robichaud, M., & Debonnel, G. (2005). Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats. Journal of Neuroendocrinology, 17, 179–185.CrossRefPubMedGoogle Scholar
  101. Roesch, D. M. (2006). Effects of selective estrogen receptor agonists on food intake and body weight gain in rats. Physiology & Behavior, 87, 39–44.CrossRefGoogle Scholar
  102. Rogers, P. J., & Blundell, J. E. (1979). Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects. Psychopharmacology, 66, 159–165.CrossRefPubMedGoogle Scholar
  103. Rogers, N. H., Perfield, J. W., 2nd, Strissel, K. J., Obin, M. S., & Greenberg, A. S. (2009). Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology, 150(5), 2161–2168.CrossRefPubMedPubMedCentralGoogle Scholar
  104. Rowland, N. E., & Carlton, J. (1986). Neurobiology of an anorectic drug: Fenfluramine. Progress in Neurobiology, 27, 13–62.CrossRefPubMedGoogle Scholar
  105. Rowland, N. E., Rokadia, S., Green, D. J., & Robertson, K. (2004). Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine. Pharmacology, Biochemistry, and Behavior, 77, 541–546.CrossRefPubMedGoogle Scholar
  106. Saito, K., Cao, X., He, Y., & Xu, Y. (2015). Progress in the molecular understanding of central regulation of body weight by estrogens. Obesity (Silver Spring), 23, 919–926.CrossRefGoogle Scholar
  107. Saito, K., He, Y., Yang, Y., Zhu, L., Wang, C., Xu, P., Hinton, A. O., Yan, X., Zhao, J., Fukuda, M., et al. (2016). PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice. Scientific Reports, 6, 23459.CrossRefPubMedPubMedCentralGoogle Scholar
  108. Saller, C. F., & Stricker, E. M. (1976). Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Science, 192, 385–387.CrossRefPubMedGoogle Scholar
  109. Santollo, J., Wiley, M. D., & Eckel, L. A. (2007). Acute activation of ER alpha decreases food intake, meal size, and body weight in ovariectomized rats. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 293, R2194–R2201.CrossRefPubMedGoogle Scholar
  110. Santollo, J., Torregrossa, A. M., & Eckel, L. A. (2011). Estradiol acts in the medial preoptic area, arcuate nucleus, and dorsal raphe nucleus to reduce food intake in ovariectomized rats. Hormones and Behavior, 60, 86–93.CrossRefPubMedPubMedCentralGoogle Scholar
  111. Schlenker, E. H., & Hansen, S. N. (2006). Sex-specific densities of estrogen receptors alpha and beta in the subnuclei of the nucleus tractus solitarius, hypoglossal nucleus and dorsal vagal motor nucleus weanling rats. Brain Research, 1123, 89–100.CrossRefPubMedGoogle Scholar
  112. Sharma, G., Hu, C., Brigman, J. L., Zhu, G., Hathaway, H. J., & Prossnitz, E. R. (2013). GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state. Endocrinology, 154, 4136–4145.CrossRefPubMedPubMedCentralGoogle Scholar
  113. Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994). Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. The New England Journal of Medicine, 331, 1056–1061.CrossRefPubMedGoogle Scholar
  114. Sohn, J. W., Xu, Y., Jones, J. E., Wickman, K., Williams, K. W., & Elmquist, J. K. (2011). Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels. Neuron, 71, 488–497.CrossRefPubMedPubMedCentralGoogle Scholar
  115. Tartaglia, L. A. (1997). The leptin receptor. The Journal of Biological Chemistry, 272, 6093–6096.CrossRefPubMedGoogle Scholar
  116. Thammacharoen, S., Lutz, T. A., Geary, N., & Asarian, L. (2008). Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology, 149, 1609–1617.CrossRefPubMedGoogle Scholar
  117. Trayhurn, P., Thurlby, P. L., & James, W. P. (1977). Thermogenic defect in pre-obese ob/ob mice. Nature, 266, 60–62.CrossRefPubMedGoogle Scholar
  118. Tschop, M., Smiley, D. L., & Heiman, M. L. (2000). Ghrelin induces adiposity in rodents. Nature, 407, 908–913.CrossRefPubMedGoogle Scholar
  119. Vaisse, C., Clement, K., Guy-Grand, B., & Froguel, P. (1998). A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genetics, 20, 113–114.CrossRefPubMedGoogle Scholar
  120. Wallen, W. J., Belanger, M. P., & Wittnich, C. (2001). Sex hormones and the selective estrogen receptor modulator tamoxifen modulate weekly body weights and food intakes in adolescent and adult rats. The Journal of Nutrition, 131, 2351–2357.CrossRefPubMedGoogle Scholar
  121. Wang, C., Dehghani, B., Magrisso, I. J., Rick, E. A., Bonhomme, E., Cody, D. B., Elenich, L. A., Subramanian, S., Murphy, S. J., Kelly, M. J., et al. (2008). GPR30 contributes to estrogen-induced thymic atrophy. Molecular Endocrinology, 22, 636–648.CrossRefPubMedGoogle Scholar
  122. Williams, D. L., & Schwartz, M. W. (2005). The melanocortin system as a central integrator of direct and indirect controls of food intake. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 289, R2–R3.CrossRefPubMedGoogle Scholar
  123. Wise, P. M., Scarbrough, K., Weiland, N. G., & Larson, G. H. (1990). Diurnal pattern of proopiomelanocortin gene expression in the arcuate nucleus of proestrous, ovariectomized, and steroid-treated rats: A possible role in cyclic luteinizing hormone secretion. Molecular Endocrinology, 4, 886–892.CrossRefPubMedGoogle Scholar
  124. Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy, K. G., Dhillo, W. S., Ghatei, M. A., & Bloom, S. R. (2001a). Ghrelin enhances appetite and increases food intake in humans. The Journal of Clinical Endocrinology and Metabolism, 86, 5992.CrossRefPubMedGoogle Scholar
  125. Wren, A. M., Small, C. J., Abbott, C. R., Dhillo, W. S., Seal, L. J., Cohen, M. A., Batterham, R. L., Taheri, S., Stanley, S. A., Ghatei, M. A., et al. (2001b). Ghrelin causes hyperphagia and obesity in rats. Diabetes, 50, 2540–2547.CrossRefPubMedGoogle Scholar
  126. Wu, M. V., Manoli, D. S., Fraser, E. J., Coats, J. K., Tollkuhn, J., Honda, S., Harada, N., & Shah, N. M. (2009). Estrogen masculinizes neural pathways and sex-specific behaviors. Cell, 139, 61–72.CrossRefPubMedPubMedCentralGoogle Scholar
  127. Xu, A. W., Kaelin, C. B., Morton, G. J., Ogimoto, K., Stanhope, K., Graham, J., Baskin, D. G., Havel, P., Schwartz, M. W., & Barsh, G. S. (2005). Effects of hypothalamic neurodegeneration on energy balance. PLoS Biology, 3, e415.CrossRefPubMedPubMedCentralGoogle Scholar
  128. Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., et al. (2011a). Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metabolism, 14, 453–465.CrossRefPubMedPubMedCentralGoogle Scholar
  129. Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., et al. (2011b). Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metabolism, 14, 453–465.CrossRefPubMedPubMedCentralGoogle Scholar
  130. Yaswen, L., Diehl, N., Brennan, M. B., & Hochgeschwender, U. (1999). Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nature Medicine, 5, 1066–1070.CrossRefPubMedGoogle Scholar
  131. Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998). A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nature Genetics, 20, 111–112.CrossRefPubMedGoogle Scholar
  132. Yepuru, M., Eswaraka, J., Kearbey, J. D., Barrett, C. M., Raghow, S., Veverka, K. A., Miller, D. D., Dalton, J. T., & Narayanan, R. (2010). Estrogen receptor-{beta}-selective ligands alleviate high-fat diet- and ovariectomy-induced obesity in mice. The Journal of Biological Chemistry, 285, 31292–31303.CrossRefPubMedPubMedCentralGoogle Scholar
  133. Zhan, C., Zhou, J., Feng, Q., Zhang, J. E., Lin, S., Bao, J., Wu, P., & Luo, M. (2013). Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. The Journal of Neuroscience, 33, 3624–3632.CrossRefPubMedGoogle Scholar
  134. Zhu, L., Xu, P., Cao, X., Yang, Y., Hinton, A. O., Jr., Xia, Y., Saito, K., Yan, X., Zou, F., Ding, H., et al. (2015). The ERalpha-PI3K cascade in proopiomelanocortin progenitor neurons regulates feeding and glucose balance in female mice. Endocrinology, 156, 4474–4491.CrossRefPubMedPubMedCentralGoogle Scholar
  135. Zigman, J. M., Nakano, Y., Coppari, R., Balthasar, N., Marcus, J. N., Lee, C. E., Jones, J. E., Deysher, A. E., Waxman, A. R., White, R. D., et al. (2005). Mice lacking ghrelin receptors resist the development of diet-induced obesity. The Journal of Clinical Investigation, 115, 3564–3572.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.USDA/ARS Children’s Nutrition Research CenterDepartment of Pediatrics, Department of Molecular and Cellular Biology, Baylor College of MedicineHoustonUSA

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