3639 Vet Med Basic Science Bldg
Department of Comparative Biosciences
2001 S. Lincoln Ave
Urbana, IL 61802
Estradiol, endocrine disruptors, and biological rhythms
My work focuses on the influence of estrogen on the expression of circadian rhythms. In rodents gonadal steroids modify the phase, amplitude and period of circadian rhythms. Ovarian hormones appear to have a similar effect in women as diurnal and circadian rhythms including sleep-wake cycles and endocrine rhythms (cortisol, melatonin) change between the follicular and luteal phases of the reproductive cycle. Sex differences in circadian rhythms exist and women are more likely than men to experience insomnia, and women undergoing the menopausal transition have significant disturbances in their sleep onset, quality, and efficiency. Hormone replacement therapy alleviates some of these problems. Despite the gender disparities in sleep-wake patterns, and the known sex differences in circadian rhythms in both rodents and humans, relatively little work has elucidated the specific role of ovarian hormones. We use three transgenic mouse models to examine the interplay of estrogen on circadian rhythms: aromatase knock-out mice which cannot make estrogen, estrogen receptor 1 knockout mice which make estrogen but are missing one of the receptors, and non-traditional estrogen receptor knock-in mice which have an altered estrogen receptor which only allows estrogen to act via 2nd messenger pathways.
Additionally my interest in hormone regulation of circadian rhythms has been extended to understanding the impact of endocrine disrupting chemicals on biological timekeeping. Humans are exposed to a number of endocrine disrupting chemicals (EDCs) that perturb physiology and have an adverse impact on human health. Despite the chronic exposure to environmental toxicants and the fundamental importance of the timekeeping system for maintaining homeostasis, it remains unknown how EDCs affect the timekeeping physiology in adults, in animals exposed to EDCs in development, or if there are sex differences in the adverse effects of EDCs on circadian rhythms. Our global hypothesis is that EDCs adversely impact the timekeeping systems by disrupting the 24-hour patterns of behavioral rhythms and gene expression in the master clock and peripheral organs. We test this hypothesis by feeding mice EDCs and monitoring their changes in rhythmic behaviors and gene expression.
Royston, S.E., D. Bunick, and M.M. Mahoney, Estradiol exposure early in life programs daily and circadian activity rhythms in adult mice. J Neuroendocrinol, 2015.
Blattner, M.S. and M.M. Mahoney, Changes in estrogen receptor signaling alters the timekeeping system in male mice. Behav Brain Res, 2015. 294: p. 43-9.
Royston, S.E., N. Yasui, A.G. Kondilis, S.V. Lord, J.A. Katzenellenbogen, and M.M. Mahoney, ESR1 and ESR2 Differentially Regulate Daily and Circadian Activity Rhythms in Female Mice. Endocrinology, 2014. 155(7): p. 2613-23.
Blattner, M.S. and M.M. Mahoney, Estrogen receptor 1 modulates circadian rhythms in adult female mice. Chronobiol Int, 2014. 31(5): p. 637-44.
Ziv-Gal, A., J.A. Flaws, M.M. Mahoney, S.R. Miller, H.A. Zacur, and L. Gallicchio, Genetic polymorphisms in the aryl hydrocarbon receptor-signaling pathway and sleep disturbances in middle-aged women. Sleep Med, 2013. 14(9): p. 883-7.
Blattner, M.S. and M.M. Mahoney, Photic phase-response curve in 2 strains of mice with impaired responsiveness to estrogens. J Biol Rhythms, 2013. 28(4): p. 291-300.
Blattner, M.S. and M.M. Mahoney, Circadian parameters are altered in two strains of mice with transgenic modifications of estrogen receptor subtype 1. Genes Brain Behav, 2012. 11: p. 828-836.
Mong, J.A., et al., Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci. 31(45): p. 16107-16.
Brockman, R., Bunick, D. and M. Mahoney. 2011. Estradiol deficiency during development modulates the expression of circadian and daily rhythms in male and female aromatase knock out mice. Hormones and Behavior. 60(4), p. 439-47.
Steinberg, G. Byron, J. and M. Mahoney. 2011. A retrospective study of circadian and seasonal presentations of dogs with congestive heart failure. Journal of Veterinary Emergency and Critical Care. In Press.
Mahoney, M.M. Rossi, B.V, Hagenauer, M. H. and T. Lee. 2011. Characterization of the estrous cycle in Octodon degus. Biology of Reproduction. 84(4):664-71.
Mahoney, M.M. and V. Padmanabhan. 2010. Developmental programming: Impact of fetal exposure to endocrine disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus. Toxicology and Applied Pharmacology. 247(2):98-104.
Mahoney, M.M. 2010. Shift work, jet lag, and female reproduction. International Journal of Endocrinology. Epub 2010 March 8.
Mahoney, M.M., Ramanathan, C., Hagenauer, M.H. Thompson, R. Lee, T., and L. Smale. 2009. Daily rhythms and sex differences in vasoactive intestinal polypeptide, VIPR2 receptor, and arginine vasopressin mRNA in the suprachiasmatic nucleus of a diurnal rodent, Arvicanthis niloticus. European Journal of Neuroscience. 30(8): 1537-43.
Mahoney, M.M., Smale L., and T. Lee. 2009. Daily immediate early gene expression in the suprachiasmatic nucleus of male and female Octodon degus. Chronobiology International. 26(5): 821-837
Gorton, L.M., Mahoney, M.M., Magorien, J.E., Lee, T.M. and R.I. Wood. 2009. Estrogen receptor immunoreactivity in late-gestation fetal lambs. Biology of Reproduction. 80(6): 1152-1159.
Mahoney, M.M., Ramanathan, C. and L. Smale. 2007. Tyrosine hydroxylase positive neurons and their contacts with vasoactive intestinal peptide-containing fibers in the hypothalamus of the diurnal murid rodent, Arvicanthis niloticus. Journal of Chemical Neuroanatomy 33:131-139
Hummer, DH, Jechura T., Mahoney, M.M., and T. Lee. 2007. Gonadal hormone effects on entrained and free-running circadian activity rhythms in the developing diurnal rodent, Octodon degus. American Journal of Physiology 292(1):R586-597
Jechura, T.J., Mahoney, M.M, Stimpson, C.D. and T. Lee. 2006. Odor specific effects on re-entrainment following phase advances in the diurnal rodent Octodon degus American Journal of Physiology 292(6):R1808-1816
Mahoney, M.M. and L. Smale. 2005. Arginine vasopressin and vasoactive intestinal polypeptide fibers make appositions with gonadotropin releasing hormone and estrogen receptor cells in the diurnal rodent Arvicanthis niloticus. Brain Research 1049:156-164