Faculty Profile

Fields of Study

Developmental Neuroendocrinology

Areas of Focus

Neurobiology & Animal Physiology

Research Interest

Molecular mechanisms of hormone action in brain development, functional and structural evolution of neuropeptides, developmental plasticity and long term consequences of early life stress.

About Robert Denver

Dr. Denver's research is on the hormonal control of postembryonic development. Current focus is on two primary topics: (1) the molecular basis of hormone action in brain development, and (2) the role of stress hormones in mediating developmental plasticity. For the first topic, gene expression screening is used to identify genes that are differentially regulated by hormones in the developing central nervous system, using the frog Xenopus, rodents, and neural cell lines. Biochemical, molecular and transgenesis techniques are used to understand the functional properties of cloned gene products. For the second topic, studies of the role of central nervous stress centers in mediating environmental effects on postembryonic development have found that the stress neuropeptide, corticotropin-releasing hormone, controls amphibian metamorphosis. This research includes studying the cellular and molecular basis for signal transduction in the neuroendocrine system during spontaneous and environmentally-induced metamorphosis, and is integrated with studies on the ecology of metamorphosis.

Dr. Denver received his Ph.D. from the University of California at Berkeley in 1989.

Publications

Denver, R.J. and Williamson, K.E. (2009). "Identification of a thyroid hormone response element in the mouse Krüppel-like factor 9 gene to explain its postnatal expression in the brain." Endocrinology 150:3935-3943. Supplemental Data: http://endo.endojournals.org/cgi/content/full/en.2009-0050/DC1

Denver, R.J., Hopkins, P.M., McCormick, S.D., Propper, C.R., Riddiford, L., Sower, S.A. and Wingfield, J.C. (2009). "Comparative endocrinology in the 21^st century." Integrative and Comparative Biology doi: 10.1093/icb/icp082. Please contact rdenver@umich.edu for access to PDF reprint (Secure Publications link) .

Denver, R.J. (2009). "Endocrinology of Complex Life Cycles: Amphibians." In: "Hormones, Brain and Behavior" D. Pfaff, A. Arnold, A. Etgen, S. Fahrbach, R. Moss & R. Rubin (eds.) 2nd edition, Elsevier. Please contact rdenver@umich.edu for access to PDF reprint (Secure Publications link) .

Denver R.J. (2009). "Stress hormones mediate environment-genotype interactions during amphibian development." General and Comparative Endocrinology 164:20-31. Please contact rdenver@umich.edu for access to PDF reprint (Secure Publications link).

Denver, R.J. (2009). "Structural and functional evolution of vertebrate neuroendocrine stress systems." Annals of the New York Academy of Sciences 1163: 1-16.

Roubos, E., Kuribara, M., Kuipers-Kwant, F., Coenen, T., Meijer, K., Cruijsen, P. and Denver, R.J. (2009). "Dynamics of glucocorticoid and mineralocorticoid receptors in the Xenopus laevis pituitary pars intermedia." Annals of the New York Academy of Sciences 1163: 292-295.

Fraker, M.E., Cuddapah, V., McCollum, S.A., Hu, F., Relyea, R., Hempel, J. and Denver, R.J. (2009). "Characterization of an alarm pheromone secreted by amphibian tadpoles that induces behavioral inhibition and suppression of the neuroendocrine stress axis." Hormones and Behavior 55:520-529. Please contact rdenver@umich.edu for access to PDF reprint (Secure Publications link).

Bonett, R.M.*, Hu, F.*, Bagamasbad, P. and Denver, R.J. (2009). "Stressor and glucocorticoid-dependent induction of the immediate early gene Krüppel-like factor 9: implications for neural development and plasticity." Endocrinology 150:1757–1765. *Co-first authors

Denver, R.J.,Hu, F., Scanlan, T.S., Furlow, J.D. (2009). "Thyroid hormone receptor subtype specificity for hormone-dependent neurogenesis in Xenopus laevis." Developmental Biology 326:155-168. Please contact rdenver@umich.edu for access to PDF reprint (Secure Publications link).

Hu, F., Crespi, E.J. and Denver, R.J. (2008). "Programming neuroendocrine stress axis activity by exposure to glucocorticoids during postembryonic development of the frog Xenopus laevis." Endocrinology 149:5470-5481 . (Cited in Faculty of 1000 Biology, 31 Oct 2008 http://www.f1000biology.com/article/id/1124030/evaluation)

Denver, R.J. (2008). "Chordate metamorphosis: Ancient control by iodothyronines." Current Biology 18:R567-R569.

Hen, G., Yosefi, S., Ronin, A., Einat, P., Rosenblum, C.I., Denver, R.J. and Friedman-Einat, M. (2008). "Monitoring leptin activity using the chicken leptin receptor." Journal of Endocrinology 197:325-333.

Yao, M., Schulkin, J. and Denver, R.J. (2008). "Evolutionarily conserved glucocorticoid regulation of corticotropin-releasing factor expression." Endocrinology 149:2352-2360. (Article featured in Endocrine News March 2008) Read Publication

Yao, M., Hu, F. and Denver, R.J. (2008). "Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis." Journal of Comparative Neurology 508:967-982.

Bagamasbad, P., Howdeshell, K.L., Sachs, L.M., Demeneix, B.A. and Denver, R.J. (2008). "A role for basic transcription element binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor beta." Journal of Biological Chemistry 283 2275-2285. Read Publication

Yao, M. and Denver, R.J. (2007). "Regulation of vertebrate corticotropin-releasing factor genes." General and Comparative Endocrinology 153:200-216. Read Publication

Yao,M., Stenzel-Poore, M. and Denver, R.J. (2007). "Structural and functional conservation of vertebrate corticotropin-releasing factor genes: evidence for a critical role for a conserved cyclic AMP response element." Endocrinology 148:2518-2531. Supplemental data at http://endo.endojournals.org/cgi/content/full/en.2006-1413/DC1 Read Publication

Denver, R.J. (2007). "Endocannabinoids link rapid, membrane-mediated corticosteroid actions to behavior." Endocrinology 148:490-492. Read Publication

Okada, R., Miller, M.F., Yamamoto, K., De Groef, B. Denver, R.J. and Kikuyama, S. (2007). "Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF-induced thyrotropin release by the amphibian pituitary gland." General and Comparative Endocrinology 150:437-444. Read Publication

Safi, R., Vlaeminck-Guillem, V., Duffraisse, M., Seugnet, I., Plateroti, M., Margotat, A., Duterque-Coquillaud, M., Crespi, E.J., Denver, R.J., Demeneix, B, & Laudet, V. (2006). "Pedomorphosis revisited: Thyroid hormone receptors are functional in Necturus maculosus." Evolution and Development 8:3, 284-292. Read Publication

Crespi, E.J. and Denver, R.J. (2006). "Leptin (ob gene) of the South African clawed frog Xenopus laevis." Proceedings of the National Academy of Sciences, USA 103:10092-10097. (Article featured in NSF Discoveries) Supporting information at: http://www.pnas.org.proxy.lib.umich.edu/content/103/26/10092/suppl/DC1 Read Publication

Denver, R.J. and Crespi, E.J. (2006). "Stress hormones and human developmental plasticity: lessons from tadpoles." Neoreviews 7(4):183-188T. Read Publication

Boorse, G.C., Kholdani, C.A., Seasholtz, A.F. and Denver, R.J. (2006). "Corticotropin-releasing factor is cytoprotective in Xenopus tadpole tail: Integration of ligand, receptor and binding protein in tail muscle cell survival." Endocrinology 147:1498-1507. Read Publication

Boorse, G.C. and Denver, R.J. (2006). "Widespread tissue distribution and diverse functions of corticotropin-releasing factor and related peptides." General and Comparative Endocrinology 146:9-18. Read Publication

Rot-Nikcevic, I., Denver R.J. and Wassersug, R.J. (2005). "The influence of visual and tactilestimulation on growth and metamorphosis in anuran larvae." Functional Ecology 19:1008-1016. Read Publication

Calle, M., Wang, L., Kozicz, T., Denver, R.J., Barendregt, H. and Roubos, E.W. (2005). "Evidence that urocortin I acts as a neurohormone to stimulate MSH release in the toad Xenopus laevis." Brain Research 1040:14-28. Read Publication

Crespi, E.J. and Denver, R.J. (2005). "Ancient origins of human developmental plasticity." American Journal of Human Biology 17:44-54. Read Publication

Vandenborne, K., De Groef, B., Geelissen, S.M.E., Boorse, G.C., Denver, R.J., Kühn, E.R., Darras, V.M. and Van der Geyten, S. (2005). "Molecular cloning and developmental expression of the corticotropin-releasing factor in the chicken." Endocrinology 146:301-308. Read Publication

Boorse, G.C., Crespi, E.J., Dautzenberg, F.M. and Denver, R.J. (2005). "Urocortins of the South African clawed frog Xenopus laevis: Conservation of structure and function in tetrapod evolution." Endocrinology 146:4851-4860. Supplemental data: http://endo.endojournals.org/cgi/data/en.2005-0497/DC1/3 Read Publication

Crespi, E.J. and Denver, R.J. (2005). "Roles of stress hormones in food intake regulation throughout the life cycle of anuran amphibians." Comparative Biochemistry and Physiology 141(4):381-390. Read Publication

Yao, M., Westphal, N. and Denver, R.J. (2004). "Neuroanatomical distribution and stressor-induced activation of central corticotropin-releasing factor neurons in Xenopus laevis." Journal of Neuroendocrinology 16:880-893. Read Publication

Crespi, E.J. and Denver, R.J. (2004). "Ontogeny of corticotropin-releasing hormone effects on locomotion and foraging in the Western spadefoot toad (Spea hammondii)." Hormones and Behavior 46:399-410. Read Publication

Manzon, R. and Denver, R.J. (2004). "Regulation of pituitary thyrotropin gene expression during Xenopus metamorphosis: negative feedback is functional throughout metamorphosis. ." Journal of Endocrinology 182:273-285. Read Publication

Boorse, G.C. and Denver, R.J. (2004). "Expression and hypophysiotropic actions of corticotropin releasing factor in Xenopus laevis." General and Comparative Endocrinology 137:272-282. Read Publication

Denver, R.J. (2004). "Corticotropin-releasing hormone." Encyclopedia of Endocrinology and Endocrine Diseases. (Ed. Luciano Martini) pp. 580-583. Read Publication

Krain, L.P. and Denver, R.J. (2004). "Developmental expression and hormonal regulation of glucocorticoid and thyroid hormone receptors during metamorphosis in Xenopus laevis. ." Journal of Endocrinology 181:91-104. Read Publication

Crespi, E.J., Vaudry, H. and Denver, R.J. (2004). "Roles of corticotropin-releasing hormone, neuropeptide Y and corticosterone in the regulation of food intake in Xenopus laevis." Journal of Neuroendocrinology 16:279-288. Read Publication

Boorse, G.C. and Denver, R.J. (2004). "Endocrine mechanisms underlying plasticity in metamorphic timing in spadefoot toads." Integrative and Comparative Biology 43(5):646-657. Read Publication

Amiel-Tison, C., Cabrol, D., Denver, R.J., Jarreau, P.H., Papiernik, E. and Piazza, P.V. (2004). "Fetal adaptation to stress - part I: Acceleration of fetal maturation and earlier birth triggered by placental insufficiency in humans." Early Human Development 78:15-27. Read Publication

Amiel-Tison, C., Cabrol, D., Denver, R.J., Jarreau, P.H., Papiernik, E. and Piazza, P.V. (2004). "Fetal adaptation to stress - part II: Evolutionary aspects. Stress-induced hippocampal damage. Longterm effects on behavior. Consequences on adult health." Early Human Development 78:81-94. Read Publication

Hoopfer, E.D., Huang, L. and Denver, R.J. (2002). "Basic transcription element binding protein is a thyroid hormone-regulated transcription factor expressed during metamorphosis in Xenopus laevis. ." Development, Growth and Differentiation 44:365-381. Read Publication

Seasholtz, A.F., Valverde, R.A. and Denver, R.J. (2002). "Corticotropin-releasing hormone-binding protein (CRH-BP): Biochemistry and function from fishes to mammals." Journal of Endocrinology 175:89-97. Read Publication

Burger, M.F. and Denver, R.J. (2002). "Plasma thyroid hormone concentrations in a wintering passerine bird: Their relationship to geographic variation, environmental factors, metabolic rate and body fat. ." Physiological and Biochemical Zoology 75:187-199. Read Publication

Glennemeier, K.A. and Denver, R.J. (2002). "Small changes in whole-body corticosterone content affect larval Rana pipiens fitness components." General and Comparative Endocrinology 127:16-25. Read Publication

Glennemeier, K.A. and Denver, R.J. (2002). "Developmental changes in interrenal responsiveness in anuran amphibians." Integrative and Comparative Biology 42:565-573. Read Publication

Denver, R.J., Boorse, G.C. and Glennemeier, K.A. (2002). "Endocrinology of complex life cycles: Amphibians." In: "Hormones, Brain and Behavior" D. Pfaff, A. Arnold, A. Etgen, S. Fahrbach, R. Moss & R. Rubin (eds.) Rubin. Vol. 2. Academic Press, Inc.: San Diego. pp. 469-513. Read Publication

Boorse, G.C. and Denver, R.J. (2002). "Acceleration of Ambystoma tigrinum metamorphosis by corticotropin-releasing hormone. ." Journal of Experimental Zoology 293:94-98. Read Publication

Cayrou, C., Denver, R.J. and Puymirat, J. (2002). "Suppression of BTEB in brain neuronal cultures inhibits thyroid hormone-induced neurite branching." Endocrinology 143:2242-2249. Read Publication

Glennemeier, K.A. and Denver, R.J. (2002). "Role for corticoids in mediating the response of Rana pipiens tadpoles to intraspecific competition." Journal of Experimental Zoology 292:32-40. Read Publication

Valverde, R.A., Seasholtz, A.F., Cortright, D.N. and Denver, R.J. (2001). "Biochemical characterization and expression analysis of the Xenopus laevis corticotropin-releasing hormone binding protein." Molecular and Cellular Endocrinology 173:29-40. Read Publication

Glennemeier, K.A. and Denver, R.J. (2001). "Sublethal effects of chronic exposure to an organochlorine compound on northern leopard frog (Rana pipiens) tadpoles." Environmental Toxicology 16:287-297. Read Publication

Denver, R.J. (1999). "Evolution of the corticotropin-releasing hormone signaling system and its role in stress-induced developmental plasticity." Annals of the New York Academy of Sciences 897:46-53. Read Publication

Denver, R.J., Ouellet, L., Furling, D., Kobayashi, A., Fujii-Kuriyama, Y. and Puymirat, J. (1999). "Basic transcription element binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system: Evidence for a role in neurite outgrowth. ." Journal of Biological Chemistry 274:23128-23134. Read Publication

Denver, R.J. (1998). "Molecular basis of thyroid hormone-dependent central nervous system remodeling during amphibian metamorphosis." Comparative Biochemistry and Physiology Part C 119:219-228. Read Publication

Denver, R.J. (1998). "Hormonal correlates of environmentally induced metamorphosis in the Western spadefoot toad, Scaphiopus hammondii." General and Comparative Endocrinology 110:326-336. Read Publication

Denver, R.J., Mirhadi, N. and Phillips, M. (1998). "Adaptive plasticity in amphibian metamorphosis: response of Scaphiopus hammondii tadpoles to habitat desiccation." Ecology 79:1859-1872. Read Publication

Denver, R.J. (1997). "Regulation of growth hormone secretion and action in reptiles and amphibians." Advances in Comparative Endocrinology (eds. S. Kawashima and S. Kikuyama) pp. 907-914. Read Publication

Denver, R.J. (1997). "Thyroid hormone action in brain development: Molecular biological aspects." Advances in Comparative Endocrinology (eds. S. Kawashima and S. Kikuyama) pp. 1071-1078. Read Publication

Denver, R.J., Pavgi, S. and Shi, Y.B. (1997). "Thyroid hormone-dependent gene expression program for Xenopus neural development." Journal of Biological Chemistry 272:8179-8188. Read Publication

Denver, R.J. (1997). "Environmental stress as a developmental cue: Corticotropin-releasing hormone is a proximate mediator of adaptive phenotypic plasticity in amphibian metamorphosis." Hormones and Behavior 31:169-179. Read Publication

Denver, R.J. (1997). "Proximate mechanisms of phenotypic plasticity in amphibian metamorphosis." American Zoologist 37:172-184. Read Publication

Denver, R.J. (1996). "Neuroendocrine control of amphibian metamorphosis. In: "Metamorphosis: Post-Embryonic Reprogramming of Gene Expression in Amphibian and Insect Cells."." J. R. Tata, L. I. Gilbert and E. Frieden (eds.) Academic Press. pp. 433-464. . Read Publication

Denver, R.J. (1995). "Environment-neuroendocrine interactions in the control of amphibian metamorphosis." Netherlands Journal of Zoology 45:195-200. Read Publication

Denver, R.J. and Nicoll, C.S. (1994). "Pancreatic hormones differentially regulate insulin-like growth factor(IGF)-I and IGF binding protein production by primary rat hepatocytes." Journal of Endocrinology 142:299-310. Read Publication

Denver, R.J. (1993). "Acceleration of anuran amphibian metamorphosis by corticotropin-releasing hormone-like peptides." General and Comparative Endocrinology 91:38-51. Read Publication

Edwards, C.P., Denver, R.J. and Firestone, G.L. (1993). "Glucocorticoid-inhibited production of platelet-derived growth factor A-chain requires steroid-mediated growth suppression in transformed and normal hepatic-derived cells." Endocrine Journal 1:79-86. Read Publication

Denver, R.J. and Licht, P. (1991). "Dependence of body growth on thyroid activity in turtles." Journal of Experimental Zoology 258:48-59. Read Publication

Licht, P. and Denver, R.J. (1991). "Comparative survey of plasma thyroxine binding proteins in turtles." Journal of Experimental Zoology 259:43-52. Read Publication

Denver, R.J. and Harvey, S. (1991). "Thyroidal inhibition of chicken pituitary growth hormone: alterations in secretion and accumulation of newly synthesized hormone." Journal of Endocrinology 131:39-48. Read Publication

Licht, P., Denver, R.J., Herrera, B. and Pavgi, S. (1991). "Seasonality in plasma thyroxine binding in turtles." Journal of Experimental Zoology 260:59-65. Read Publication

Denver, R.J. and Licht, P. (1991). "Several hypothalamic peptides stimulate thyrotropin and growth hormone secretion by adult turtle pituitary glands. ." Comparative Biochemistry and Physiology 100A:603-606. Read Publication

Licht, P. and Denver, R.J. (1990). "Regulation of thyrotropin secretion." In: "Progress in Comparative Endocrinology." A. Epple, C.G. Scanes and M.H. Stetson (eds.) Wiley-Liss, New York. pp. 427-432. Read Publication

Denver, R.J. and Licht, P. (1990). "Modulation of neuropeptide-stimulated pituitary hormone release in hatchling turtles." General and Comparative Endocrinology 77:107-115. Read Publication

Stamper, D.L., Denver, R.J. and Licht, P. (1990). "Effects of thyroidal status on metabolism and growth of juvenile turtles, Pseudemys scripta elegans." Comparative Biochemistry and Physiology 96A:67-73. Read Publication

Licht, P., Denver, R.J. and Stamper, D.L. (1990). "Relation of plasma thyroxine binding to thyroidal activity and determination of thyroxine binding proteins in a turtle, Pseudemys scripta." General and Comparative Endocrinology 80:238-256. Read Publication

Licht, P., Pavgi, S. and Denver, R.J. (1990). "The role of hormone binding in the cold suppression of hormone stimulation of the pituitary, thyroid and testis of the turtle." General and Comparative Endocrinology 80:381-392. Read Publication

Denver, R.J. and Licht, P. (1989). "Neuropeptides influencing pituitary hormone secretion in hatchling turtles." Journal of Experimental Zoology 251:306-315. Read Publication

Denver, R.J. and Licht, P. (1989). "Neuropeptide stimulation of thyrotropin secretion in the larval bullfrog: Evidence for a common neuroregulator of thyroid and interrenal activity during metamorphosis. ." Journal of Experimental Zoology 252:101-104. Read Publication

Licht, P., Denver, R.J. and Pavgi, S. (1989). "Temperature dependence of in vitro pituitary, gonadal and thyroid secretion in a turtle, Pseudemys scripta." General and Comparative Endocrinology 76:274-285. Read Publication

Denver, R.J. and Licht, P. (1989). "Synthetic neuropeptide antagonists stimulate in vitro thyrotropin and growth hormone secretion by hatchling turtle pituitaries." Journal of Experimental Zoology 252:169-173. Read Publication

Licht, P. and Denver, R.J. (1988). "Effects of TRH on hormone release from pituitaries of the lizard, Anolis carolinensis." General and Comparative Endocrinology 70:355-362. Read Publication

Denver, R.J. and Licht, P. (1988). "Thyroid status influences in vitro thyrotropin and growth hormone responses to thyrotropin-releasing hormone by pituitary glands of hatchling slider turtles (Pseudemys scripta elegans). ." Journal of Experimental Zoology 246:293-304. Read Publication

Denver, R.J. and Licht, P. (1988). "Thyroid hormones act at the level of the pituitary to regulate thyrotropin and growth hormone secretion in hatchling slider turtles (Pseudemys scripta elegans)." Journal of Experimental Zoology 247:146-154. Read Publication

Denver, R.J. (1988). "Several hypothalamic peptides stimulate in vitro thyrotropin secretion by pituitaries of anuran amphibians." General and Comparative Endocrinology 72:383-393. Read Publication

Scanes, C.G., Denver, R.J. and Bowen, S.J. (1986). "Effect of thyroid hormones on growth hormone secretion in broiler chickens." Poultry Science 65:384-390. Read Publication