Chapter 4 Cholesterol and steroid hormones: modulators of oxytocin receptor function
Abstract
The function and physiological regulation of the oxytocin-receptor system is strongly steroid-dependent. This is, unexpectedly, only partially reflected by the promoter sequences in the oxytocin receptor and favors the idea that posttranscriptional mechanisms may also play a significant role for the physiological regulation of the oxytocin-receptor system. Our data indicate that cholesterol acts as an allosteric modulator of the oxytocin receptor and stabilizes both membrane-associated and solubilized OT receptors in a high-affinity state for agonists and antagonists. Moreover, high-affinity OT receptors are 2-fold enriched in cholesterol-rich plasma membrane domains in HEK293 fibroblasts stably expressing the human OT receptor. Biochemical data suggest a direct and cooperative molecular interaction of cholesterol molecules with OT receptors. To localize the cholesterol interacting domain of the oxytocin receptor the C-terminal part including the last two transmembrane domains have been exchanged by the corresponding sequences of the cholecystokinin type B receptor, which is functionally not dependent on cholesterol. Concerning its ligand-binding behavior this chimeric receptor protein showed the same dependence on cholesterol and its analogues as the wild type oxytocin receptor. From mutagenesis experiments and studies with receptor chimera between the OTR and cholecystokinin type B receptor, we conclude that a major part of the cholesterol interacting domain may be localized in the first part of the oxytocin receptor, possibly in a domain nearby the agonist binding site. Progesterone is considered to be essential to maintain the uterine quiescence. High concentrations of progesterone (> 10 microM) attenuate or block the signaling of several GPCRs, including the OT receptor via a fast, reversible and non-genomic pathway. Progesterone is known to inhibit both cholesterol biosynthesis and the intracellular trafficking of cholesterol. We therefore test the hypothesis that progesterone affects the signal transduction and subdomain localization of receptors via its influence on cholesterol trafficking. Since cholesterol-rich subdomains (rafts) are considered to be organization centers for cellular signal transduction, changes of the level or distribution of cholesterol may have profound effects on receptor-mediated signaling in general. Using fluorescence recovery after photobleaching (FRAP) measurements with GFP-tagged oxytocin receptors the influence of steroids on the mobility and distribution of the oxytocin receptor in the plasma membrane was analyzed. Progesterone had no effect on the lateral mobility of the oxytocin receptor, but it led to marked inhibition of cellular motility such as vesicle trafficking and movements of filopodia. Non-genomic effects of progesterone and estradiol with respect to receptor signaling as well as the influence of cholesterol on signal transduction will be discussed in more detail.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Progesterone inhibits oxytocin receptor by repressing its synthesis.
“It has been shown that estradiol promotes oxytocin receptor binding by increasing the oxytocin receptor concentrations, whereas progesterone inhibits oxytocin receptor by repressing its synthesis (Choleris et al., 2008; Gimpl et al., 2002; Nissenson et al., 1978).”
From Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology (2014) · cites this paper as Gimpl et al., 2002
Estradiol promotes oxytocin receptor binding by increasing oxytocin receptor concentrations.
“It has been shown that estradiol promotes oxytocin receptor binding by increasing the oxytocin receptor concentrations, whereas progesterone inhibits oxytocin receptor by repressing its synthesis (Choleris et al., 2008; Gimpl et al., 2002; Nissenson et al., 1978).”
From Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology (2014) · cites this paper as Gimpl et al., 2002
Cites
Lipid rafts and signal transduction
Simons, K., & Toomre, D. K. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036052 · Cited by 6,252 · see citing works
The oxytocin receptor system: structure, function, and regulation
Gimpl, G., & Fahrenholz, F. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.629 · Cited by 3,089 · see citing works
Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor
Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., & Paul, S. M. (1986) · Science · doi:10.1126/science.2422758 · Cited by 2,225 · see citing works
Okamoto, T., Schlegel, A., Scherer, P. E., & Lisanti, M. P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5419 · Cited by 1,496 · see citing works
Purification, molecular cloning, and expression of the mammalian sigma1-binding site.
Hanner, M., Moebius, F. F., Flandorfer, A., Knaus, H. G., Striessnig, J., Kempner, E. S., & Glossmann, H. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.8072 · Cited by 906 · see citing works
Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives
Rupprecht, R., & Holsboer, F. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01399-5 · Cited by 636 · see citing works
Acute cholesterol depletion inhibits clathrin-coated pit budding
Subtil, A., Gaidarov, I., Kobylarz, K. A., Lampson, M. A., Keen, J. H., & McGraw, T. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6775 · Cited by 577 · see citing works
Steroid Binding at σ Receptors Suggests a Link Between Endocrine, Nervous, and Immune Systems
Su, T., London, E. D., & Jaffe, J. H. (1988) · Science · doi:10.1126/science.2832949 · Cited by 548 · see citing works
Klein, U., Gimpl, G., & Fahrenholz, F. (1995) · Biochemistry · doi:10.1021/bi00042a009 · Cited by 547 · see citing works
Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor.
Wu, F., Gibbs, T. T., & Farb, D. H. (1991) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)12923-4 · Cited by 534 · see citing works
Acute Activation of Maxi-K Channels ( hSlo ) by Estradiol Binding to the β Subunit
Valverde, M. A., Rojas, P., Amigo, J. D., Cosmelli, D. J., Orio, P., Bahamonde, M. I., Mann, G. E., Vergara, C., & Latorre, R. (1999) · Science · doi:10.1126/science.285.5435.1929 · Cited by 508 · see citing works
A Role for Caveolin in Transport of Cholesterol from Endoplasmic Reticulum to Plasma Membrane
Smart, E. J., Ying, Y., Donzell, W. C., & Anderson, R. G. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.29427 · Cited by 501 · see citing works
Galbiati, F., Volonté, D., Engelman, J. A., Watanabe, G., Burk, R., Pestell, R. G., & Lisanti, M. P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6633 · Cited by 471 · see citing works
Inhibition of oxytocin receptor function by direct binding of progesterone
Grazzini, E., Guillon, G., Mouillac, B., & Zingg, H. H. (1998) · Nature · doi:10.1038/33176 · Cited by 466 · see citing works
Cholesterol as Modulator of Receptor Function
Gimpl, G., Bürger, K., & Fahrenholz, F. (1997) · Biochemistry · doi:10.1021/bi963138w · Cited by 454 · see citing works
Moosmann, B., & Behl, C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.8867 · Cited by 411 · see citing works
Russell, K. S., Haynes, M. P., Sinha, D., Clerisme, E., & Bender, J. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.11.5930 · Cited by 395 · see citing works
Hisamoto, K., Ohmichi, M., Kurachi, H., Hayakawa, J., Kanda, Y., Nishio, Y., Adachi, K., Tasaka, K., Miyoshi, E., Fujiwara, N., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005036200 · Cited by 386 · see citing works
Furuchi, T., & Anderson, R. G. W. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.21099 · Cited by 374 · see citing works
Cholesterol Efflux-mediated Signal Transduction in Mammalian Sperm
Visconti, P. E., Galantino‐Homer, H. L., Ning, X., Moore, G. D., Valenzuela, J. P., Jorgez, C. J., Álvarez, J. G., & Kopf, G. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.5.3235 · Cited by 320 · see citing works
Regulation of receptor function by cholesterol
Bürger, K., Gimpl, G., & Fahrenholz, F. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000643 · Cited by 302 · see citing works
Progesterone modulates a neuronal nicotinic acetylcholine receptor.
Valera, S., Ballivet, M., & Bertrand, D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.20.9949 · Cited by 277 · see citing works
Bist, A., Fielding, P. E., & Fielding, C. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10693 · Cited by 252 · see citing works
Caffrey, J. M., & Farach‐Carson, M. C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47057-9 · Cited by 243 · see citing works
Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase
Goetz, R. M., Thatte, H. S., Prabhakar, P., Cho, M., Michel, T. M., & Golan, D. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.2788 · Cited by 234 · see citing works
Cholesterol in signal transduction
Incardona, J. P., & Eaton, S. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)00076-9 · Cited by 223 · see citing works
Estrogen Modulation of G-protein-coupled Receptors
Kelly, M. J., & Wagner, E. J. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(99)00190-3 · Cited by 221 · see citing works
Bayaa, M., Booth, R. A., Sheng, Y., & Liu, X. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220302597 · Cited by 215 · see citing works
Inverse modulation of gamma-aminobutyric acid- and glycine-induced currents by progesterone.
Wu, F., Gibbs, T. T., & Farb, D. H. (1990) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10996-6 · Cited by 212 · see citing works
Progesterone blocks cholesterol translocation from lysosomes.
Butler, J. D., Blanchette‐Mackie, J., Goldin, E., O'Neill, R. R., Carstea, G., Roff, C. F., Patterson, M. C., Patel, S., Comly, M. E., & Cooney, A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35908-8 · Cited by 169 · see citing works
Identification of XPR-1, a progesterone receptor required for Xenopus oocyte activation
Tian, J., Kim, S., Heilig, E. A., & RUDERMAN, J. V. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250492197 · Cited by 168 · see citing works
Gimpl, G., Klein, U., Reiländer, H., & Fahrenholz, F. (1995) · Biochemistry · doi:10.1021/bi00042a010 · Cited by 163 · see citing works
Endothelial Ca 2+ waves preferentially originate at specific loci in caveolin-rich cell edges
Isshiki, M., Ando, J., Korenaga, R., Kogo, H., Fujimoto, T., Fujita, T., & Kamiya, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5009 · Cited by 149 · see citing works
Functional Antagonism of Gonadal Steroids at the 5-Hydroxytryptamine Type 3 Receptor
Wetzel, C. H., Hermann, B., Behl, C., Pestel, E., Rammes, G., Zieglgänsberger, W., Holsboer, F., & Rupprecht, R. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.9.0163 · Cited by 135 · see citing works
Postina, R., Kojro, E., & Fahrenholz, F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31593 · Cited by 134 · see citing works
Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly
Murakami, K., Fellous, A., Baulieu, É.-É., & Röbel, P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3579 · Cited by 133 · see citing works
Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells
Liu, P., Li, W., Machleidt, T., & Anderson, R. G. W. (1999) · Nature Cell Biology · doi:10.1038/14067 · Cited by 118 · see citing works
Blondeau, J., & Baulieu, É.-É. (1984) · Biochemical Journal · doi:10.1042/bj2190785 · Cited by 110 · see citing works
Rankin, S. E., Addona, G. H., Kloczewiak, M. A., Bugge, B., & Miller, K. W. (1997) · Biophysical Journal · doi:10.1016/s0006-3495(97)78273-0 · Cited by 110 · see citing works
Role of Sterols in Modulating the Human μ-Opioid Receptor Function in Saccharomyces cerevisiae
Lagane, B., Gaibelet, G., Meilhoc, E., Masson, J., Cézanne, L., & Lopez, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000576200 · Cited by 107 · see citing works
Rhodopsin-cholesterol interactions in bovine rod outer segment disk membranes
Albert, A. D., Young, J. E., & Yèagle, P. L. (1996) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(96)00145-9 · Cited by 105 · see citing works
Fanelli, F., Barbier, P., Zanchetta, D., Benedetti, P. G. D., & Chini, B. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.1.214 · Cited by 102 · see citing works
Membrane Cholesterol Modulates Galanin−GalR2 Interaction
Pang, L., Graziano, M. P., & Wang, S. (1999) · Biochemistry · doi:10.1021/bi990227a · Cited by 97 · see citing works
Gimpl, G., & Fahrenholz, F. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01280.x · Cited by 95 · see citing works
Progesterone Inhibits Cholesterol Biosynthesis in Cultured Cells
Metherall, J. E., Waugh, K., & Li, H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.5.2627 · Cited by 91 · see citing works
Progesterone photoaffinity labels P-glycoprotein in multidrug-resistant human leukemic lymphoblasts.
Qian, X. D., & Beck, W. T. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30575-6 · Cited by 80 · see citing works
Hoare, S., Copland, J. A., Strakova, Z., Ives, K., Jeng, Y.-J., Hellmich, M. R., & Soloff, M. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28682 · Cited by 72 · see citing works
CONCENTRATION OF PROSTAGLANDIN F2α AND STEROIDS IN THE HUMAN CORPUS LUTEUM
Swanston, I. A., McNatty, K. P., & Baird, D. T. (1977) · Journal of Endocrinology · doi:10.1677/joe.0.0730115 · Cited by 66 · see citing works
Parturition: activation of stimulatory pathways or loss of uterine quiescence?
Bernal, A. L., Rivera, J., Gn, E.-F., Phaneuf, S., & Asbóth, G. (1995) · PubMed · Cited by 66 · see citing works
Ligand-induced Cleavage of the V2 Vasopressin Receptor by a Plasma Membrane Metalloproteinase
Kojro, E., & Fahrenholz, F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6476 · Cited by 63 · see citing works
Non‐genomic effects of progesterone on the signaling function of G protein‐coupled receptors
Bürger, K., Fahrenholz, F., & Gimpl, G. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01668-3 · Cited by 60 · see citing works
Oxytocin receptors and cholesterol: interaction and regulation
Gimpl, G., Bürger, K., Politowskat, E., Ciarkowski, J., & Fahrenholz, F. (2000) · Experimental Physiology · doi:10.1111/j.1469-445x.2000.tb00006.x · Cited by 56 · see citing works
Breton, C., Chellil, H., Kabbaj-Benmansour, M., Carnazzi, E., Seyer, R., Phalipou, S., Morin, D., Durroux, T., Zingg, H. H., Barberis, C., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102073200 · Cited by 56 · see citing works
Effect of progesterone on intracellular Ca2+ homeostasis in human myometrial smooth muscle cells
Fomin, V. P., Cox, B. E., & Word, R. A. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.276.2.c379 · Cited by 55 · see citing works
Progestins block cholesterol synthesis to produce meiosis‐activating sterols
Lindenthal, B., Holleran, A. L., Aldaghlas, T., Ruan, B. H., Schroepfer, G. J., Wilson, W. K., & Kelleher, J. K. (2001) · The FASEB Journal · doi:10.1096/fj.00-0214com · Cited by 50 · see citing works
Pliška, V., Heiniger, J. P., Müller-Lhotsky, A., Pliska, P., & Ekberg, B. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75988-2 · Cited by 48 · see citing works
Simpson, E. R., & Burkhart, M. F. (1980) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(80)90333-1 · Cited by 48 · see citing works
Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets
Blackmore, P. F. (1999) · Steroids · doi:10.1016/s0039-128x(98)00109-3 · Cited by 45 · see citing works
Sen, A., Ghosh, P. K., & Mukherjea, M. (1998) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006839711587 · Cited by 29 · see citing works
Conversion of the myometrial oxytocin receptor from low to high affinity state by cholesterol.
Fahrenholz, F., Klein, U., & Gimpl, G. (1995) · PubMed · Cited by 26 · see citing works
Multiple [3H]-Oxytocin Binding Sites in Rat Myometrial Plasma Membranes
Crankshaw, D., Gaspar, V., & Plis̆ka, V. (1990) · Journal of Receptor Research · doi:10.3109/10799899009064670 · Cited by 25 · see citing works
Fast outward current controlling electrical activity in rat uterine smooth muscle during gestation.
Mironneau, J., Savineau, J., & Mironneau, C. (1981) · PubMed · Cited by 23 · see citing works
Murphy, C. R., & Dwarte, D. M. (1987) · Cells Tissues Organs · doi:10.1159/000146319 · Cited by 22 · see citing works
Effect of Mg2+ on the binding of oxytocin to sheep myometrial cells
Plis̆ka, V., & Albertin, H. K. (1991) · Biochemical Journal · doi:10.1042/bj2770097 · Cited by 17 · see citing works
Downregulation of the oxytocin receptor on cultured astroglial cells
Guénot, D., & Strosser, M. T. (1995) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1995.268.2.c413 · Cited by 17 · see citing works
A biochemical-morphological study on microvillus plasma membrane development
Mazzanti, L., Staffolani, R., Cester, N., Romaninï, C., Pugnaloni, A., Mattioli‐Belmonte, M., Salvolini, E., Brunelli, M. A., & Biagini, G. (1994) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(94)90148-1 · Cited by 16 · see citing works
Liu, X. J., & RUDERMAN, J. V. (2003) · Springer eBooks · doi:10.1007/978-1-4615-0339-2_11 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Effects of intranasal oxytocin on emotional face processing in women
Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.06.016 · Cited by 521 · see citing works
Role of cholesterol in the function and organization of G-protein coupled receptors
Pucadyil, T. J., & Chattopadhyay, A. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.02.002 · Cited by 296 · see citing works
Membrane Cholesterol in the Function and Organization of G-Protein Coupled Receptors
Paila, Y. D., & Chattopadhyay, A. (2010) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-8622-8_16 · Cited by 195 · see citing works
Jafurulla, M., Tiwari, S., & Chattopadhyay, A. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.031 · Cited by 174 · see citing works
Membrane Protein–Lipid Interactions Probed Using Mass Spectrometry
Bolla, J. R., Agasid, M. T., Mehmood, S., & Robinson, C. V. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-013118-111508 · Cited by 175 · see citing works
Specificity of Intramembrane Protein-Lipid InteractionsPreprint
Contreras, F. ‐., Ernst, A. M., Wieland, F., & Brügger, B. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004705 · Cited by 167 · see citing works
Cholesterol Biosynthesis and Homeostasis in Regulation of the Cell Cycle
Singh, P., Saxena, R., Srinivas, G., Pande, G., & Chattopadhyay, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058833 · Cited by 140 · see citing works
Interaction between oestrogen and oxytocin on hypothalamic-pituitary-adrenal axis activity
Ochedalski, T., Subburaju, S., Wynn, P. C., & Aguilera, G. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01525.x · Cited by 133 · see citing works
Sex differences in fear extinction
Velasco, E. R., Florido, A., Milad, M. R., & Andero, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.020 · Cited by 125 · see citing works
The role of cholesterol in rod outer segment membranes
ALBERT, A., & Boesze‐Battaglia, K. (2005) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.02.001 · Cited by 120 · see citing works
Are specific nonannular cholesterol binding sites present in G-protein coupled receptors?
Paila, Y. D., Tiwari, S., & Chattopadhyay, A. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.11.020 · Cited by 118 · see citing works
Hormonal Physiology of Childbearing: Evidence and Implications for Women, Babies, and Maternity Care
Buckley, S. J. (2015) · Issue Lab (Candid) · Cited by 113 · see citing works
Autism spectrum disorders: The quest for genetic syndromes
Zafeiriou, D., Ververi, A., Dafoulis, V., Kalyva, E., & Vargiami, E. (2013) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32152 · Cited by 104 · see citing works
Ligand-Independent Activation of the EGFR by Lipid Raft Disruption
Lambert, S., Vind-Kezunovic, D., Karvinen, S., & Gniadecki, R. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700168 · Cited by 104 · see citing works
Paila, Y. D., & Chattopadhyay, A. (2008) · Glycoconjugate Journal · doi:10.1007/s10719-008-9218-5 · Cited by 100 · see citing works
Amphotericin B inhibits entry of Leishmania donovani into primary macrophages
Paila, Y. D., Saha, B., & Chattopadhyay, A. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.07.099 · Cited by 84 · see citing works
Autism: The role of cholesterol in treatment
Aneja, A., & Tierney, E. (2008) · International Review of Psychiatry · doi:10.1080/09540260801889062 · Cited by 82 · see citing works
Smith-Lemli-Opitz Syndrome and Autism Spectrum Disorder
Bukelis, I., Porter, F. D., Zimmerman, A. W., & Tierney, E. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07020315 · Cited by 82 · see citing works
Sex-Related Differences in Plasma Oxytocin Levels in Humans
Marazziti, D., Baroni, S., Mucci, F., Piccinni, A., Moroni, I., Giannaccini, G., Carmassi, C., Massimetti, E., & Dell’Osso, L. (2019) · Clinical Practice and Epidemiology in Mental Health · doi:10.2174/1745017901915010058 · Cited by 80 · see citing works
Chang, S. W. C., & Platt, M. L. (2014) · Brain Research · doi:10.1016/j.brainres.2013.11.006 · Cited by 71 · see citing works
The role of cholesterol on the activity and stability of neurotensin receptor 1
Oates, J., Faust, B., Attrill, H. L., Harding, P., Orwick, M., & Watts, A. G. (2012) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2012.04.010 · Cited by 70 · see citing works
Buttner, A. P. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.08.029 · Cited by 67 · see citing works
The role of oxytocin in alcohol and drug abuse
King, C. E., Gano, A., & Becker, H. C. (2020) · Brain Research · doi:10.1016/j.brainres.2020.146761 · Cited by 66 · see citing works
Paila, Y. D., Tiwari, S., Sengupta, D., & Chattopadhyay, A. (2010) · Molecular BioSystems · doi:10.1039/c0mb00148a · Cited by 62 · see citing works
The effect of oxytocin on biological motion perception in dogs (Canis familiaris)
Kovács, K., Kis, A., Kanizsàr, O., Hernádi, A., Gácsi, M., & Topál, J. (2016) · Animal Cognition · doi:10.1007/s10071-015-0951-4 · Cited by 59 · see citing works
Cholesterol Binding and Cholesterol Transport Proteins:
Harris, J. R. (2010) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-8622-8 · Cited by 58 · see citing works
Kovács, K., Kis, A., Pogány, Á., Koller, D., & Topál, J. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.09.010 · Cited by 52 · see citing works
Verlinden, H., Vleugels, R., Zels, S., Dillen, S., Lenaerts, C., Crabbé, K., Spit, J., & Broeck, J. V. (2014) · Advances in insect physiology · doi:10.1016/b978-0-12-417010-0.00003-3 · Cited by 50 · see citing works
Kovács, K., Virányi, Z., Kis, A., Turcsán, B., Hudecz, Á., Marmota, M. T., Koller, D., Rónai, Z., Gácsi, M., & Topál, J. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.00435 · Cited by 44 · see citing works
The implications of P‐glycoprotein in HIV: friend or foe?
Owen, A., Chandler, B., & Back, D. J. (2005) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2005.00324.x · Cited by 44 · see citing works
Cholesterol depletion enhances adrenergic signaling in cardiac myocytes
Paila, Y. D., Jindal, E., Goswami, S. K., & Chattopadhyay, A. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.09.006 · Cited by 43 · see citing works
Oxytocin Receptor Signaling in Vascular Function and Stroke
McKay, E. C., & Counts, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.574499 · Cited by 41 · see citing works
The outcome of tactile touch on oxytocin in intensive care patients: a randomised controlled trial
Henricson, M., Berglund, A., Määttä, S., Ekman, R., & Segesten, K. M. (2008) · Journal of Clinical Nursing · doi:10.1111/j.1365-2702.2008.02324.x · Cited by 40 · see citing works
Critical Role of Membrane Cholesterol in Exocytosis Revealed by Single Platelet Study
Ge, S., White, J. G., & Haynes, C. L. (2010) · ACS Chemical Biology · doi:10.1021/cb100130b · Cited by 39 · see citing works
Pokharel, K., Peippo, J., Weldenegodguad, M., Honkatukia, M., Li, M.-H., & Kantanen, J. (2020) · Genes · doi:10.3390/genes11040415 · Cited by 38 · see citing works
Leblebicioğlu, B., Connors, J. M., & Mariotti, A. J. (2012) · Periodontology 2000 · doi:10.1111/j.1600-0757.2011.00440.x · Cited by 37 · see citing works
Regulation of EGFR activation and signaling by lipids on the plasma membrane
Kim, D., Triet, H. M., & Ryu, S. H. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101115 · Cited by 36 · see citing works
Cholesterol in the rod outer segment: A complex role in a “simple” system
Albert, A. D., Alexander, D., & Boesze‐Battaglia, K. (2016) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2016.04.008 · Cited by 37 · see citing works
Progesterone inhibition of oxytocin signaling in endometrium
Bishop, C. V. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00138 · Cited by 35 · see citing works
Computational drug repositioning based on side-effects mined from social media
Nugent, T., Plachouras, V., & Leidner, J. L. (2016) · PeerJ Computer Science · doi:10.7717/peerj-cs.46 · Cited by 34 · see citing works
Riff, J. D., Callahan, J. W., & Sherman, P. M. (2005) · Infection and Immunity · doi:10.1128/iai.73.11.7113-7125.2005 · Cited by 34 · see citing works
Hsia, C., Richards, M. J., & Daniel, S. (2015) · Analytical Methods · doi:10.1039/c5ay00599j · Cited by 31 · see citing works
Singh, P., Saxena, R., Paila, Y. D., Jafurulla, M., & Chattopadhyay, A. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2009.07.004 · Cited by 30 · see citing works
Florea, T., Palimariciuc, M., Cristofor, A. C., Dobrin, I., Chiriță, R., Bîrsan, M., Dobrin, R., & Pădurariu, M. (2022) · Medicina · doi:10.3390/medicina58070923 · Cited by 28 · see citing works
A cholesterol analog stabilizes the human β 2 -adrenergic receptor nonlinearly with temperature
Serdiuk, T., Manna, M., Zhang, C., Mari, S. A., Kulig, W., Pluháčková, K., Kobilka, B. K., Vattulainen, I., & Müller, D. J. (2022) · Science Signaling · doi:10.1126/scisignal.abi7031 · Cited by 26 · see citing works
Sensitivity of cholecystokinin receptors to membrane cholesterol content
Desai, A. J., & Miller, L. J. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00123 · Cited by 25 · see citing works
Río, R. T.-D., van den Burg, E. H., Stoop, R., & Hegoburu, C. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5030-5 · Cited by 25 · see citing works
Geiger, J., Sexton, R., Al-Sahouri, Z., Lee, M.-Y., Chun, E., Harikumar, K. G., Miller, L. J., Beckstein, O., & Liu, W. (2021) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2021.183557 · Cited by 23 · see citing works
Ellenbogen, M. A., Linnen, A., Cardoso, C., & Joober, R. (2014) · Psychophysiology · doi:10.1111/psyp.12263 · Cited by 22 · see citing works
Proteomics and regulomics: The yin and yang of functional genomics
Werner, T. (2003) · Mass Spectrometry Reviews · doi:10.1002/mas.10067 · Cited by 22 · see citing works
The role of androgens on periodontal repair in female rats
Steffens, J. P., Santana, L. C. L., Pitombo, J. C. P., Ribeiro, D. O., Albaricci, M. C. D. C., Warnavin, S. V. S. C., Kantarcı, A., & Spolidório, L. C. (2018) · Journal of Periodontology · doi:10.1002/jper.17-0435 · Cited by 18 · see citing works
Sex matters: The impact of oxytocin on healthy conditions and psychiatric disorders
Marazziti, D., Carter, C. S., Carmassi, C., Vecchia, A. D., Mucci, F., Pagni, G., Carbone, M. G., Baroni, S., Giannaccini, G., Palego, L., et al. (2022) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2022.100165 · Cited by 18 · see citing works
Loiseau, C., Cayetanot, F., Joubert, F., Perrin‐Terrin, A., Cardot, P., Fiamma, M., Frugière, A., Straus, C., & Bodineau, L. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170719104605 · Cited by 15 · see citing works
Allosteric Modulators of the Class A G Protein Coupled Receptors
Tschammer, N. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-32805-8_9 · Cited by 13 · see citing works
Effect of capsaicin on ligand binding activity of the hippocampal serotonin1A receptor
Prasad, R., Singh, P., & Chattopadhyay, A. (2008) · Glycoconjugate Journal · doi:10.1007/s10719-008-9185-x · Cited by 12 · see citing works
Non-classical mechanisms of steroid sensing in the ovary: Lessons from the bovine oxytocin model
Ivell, R., Dai, Y., Mann, N., & Anand‐Ivell, R. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.04.016 · Cited by 12 · see citing works
Melkes, B., Hejnová, L., & Novotný, J. (2016) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-016-1293-8 · Cited by 12 · see citing works
Cholesterol: A Prelate in Cell Nucleus and its Serendipity
Saxena, N., & Chandra, N. C. (2020) · Current Molecular Medicine · doi:10.2174/1566524020666200413112030 · Cited by 12 · see citing works
The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users
Lin, S., Chen, P. S., Lee, L.-T., Lee, S.-Y., Tsai, H. C., Chen, W. T., Chen, K. C., Lee, I. H., Lu, R., & Yang, Y. K. (2018) · European Addiction Research · doi:10.1159/000485563 · Cited by 11 · see citing works
Sefah, E., & Mertz, B. (2021) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.0c01174 · Cited by 9 · see citing works
Sexton, R., Fazel, M., Schweiger, M., Pressé, S., & Beckstein, O. (2025) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.4c01522 · Cited by 7 · see citing works
Jha, P., Chaturvedi, S., Bhat, R., Jain, N., & Mishra, A. K. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1961865 · Cited by 6 · see citing works
Cholesterol allosteric modulation of the oxytocin receptor
Marlow, B., Vogel, A., Kuenze, G., Pankonin, M., Reinhardt, F., Stadler, P. F., Hildebrand, P. W., & Meiler, J. (2025) · Biophysical Journal · doi:10.1016/j.bpj.2025.04.023 · Cited by 5 · see citing works
Pokharel, K., Peippo, J., Weldenegodguad, M., Honkatukia, M., Li, M.-H., & Kantanen, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/673558 · Cited by 5 · see citing works
Cholecystokinin Type 1 Receptor
Desai, A. J. (2013) · doi:10.3998/panc.2013.9 · Cited by 4 · see citing works
New Insight into Progesterone-dependent Signalization
Kociszewska, K., & Czekaj, P. (2017) · Open Pharmaceutical Sciences Journal · doi:10.2174/1874844901704010011 · Cited by 3 · see citing works
Cholesterol Deficit in Autism: Insights from Smith–Lemli–Opitz Syndrome
Aneja, A., & Tierney, E. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-489-0_3 · Cited by 3 · see citing works
Camerini, A., Rondini, M., Garrone, O., Valsuani, C., Donati, S., Siclari, O., Sgambato, A., Tartarelli, G., Vincenti, M., Mattiot, V. P., et al. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.15.8959 · Cited by 2 · see citing works
Oxytocin: physiological and pathophysiological determinants. A review
Prokhorova, O. V., Olina, A. A., Tolibova, G. K., & Tral, T. G. (2021) · Journal of obstetrics and women s diseases · doi:10.17816/jowd63825 · Cited by 2 · see citing works
Mechanism Analysis of OsZF8-Mediated Regulation of Rice Resistance to Sheath Blight
Wang, Y., Wang, H., Zhang, L., Wang, Y., Wei, S., & Wang, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115787 · Cited by 2 · see citing works
Biochemistry of autism: changes in serotonin, reelin and oxytocin
Mukaetova‐Ladinska, E. B., Westwood, J., & Perry, E. K. (2011) · Cambridge University Press eBooks · doi:10.1017/cbo9780511973918.009 · Cited by 1 · see citing works
Ivell, R., Ludwig, M., Tribe, R. M., & Anand‐Ivell, R. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64691-3 · Cited by 1 · see citing works
Malenda, A., & Nowis, D. (2013) · Via Medica Journals
Sassano, M. F. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/wwr3-7m34
Allosteric Modulators of the Class A G Protein Coupled Receptors
Tschammer, N. (2015) · Springer eBooks · doi:10.1007/978-3-319-22473-2_9
Ivell, R., Ludwig, M., Tribe, R. M., & Anand‐Ivell, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21477-6.00121-8
Huc, M., Nikolic, M., Power, L., McQuaid, R. J., & Jaworska, N. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106610
Perrin‐Terrin, A. (2018) · doi:10.70675/e19e922bz4ab1z4df2z8e00z839db7c46630
Effects of intranasal oxytocin on fear, pain and aversive memory
Silva, J. U., & Brito, I. (2026) · Neuropeptides · doi:10.1016/j.npep.2026.102618
Lioupi, A., Gavriilidou, A. F. M., & Politis, A. (2026) · Chemical Science · doi:10.1039/d6sc04457c · Cited by 1 · see citing works
Ridden, A. D. (2013) · UC Research Repository (University of Canterbury) · doi:10.26021/6519
Linnen, A. (2011) · Spectrum Research Repository (Concordia University)
- Authors
- Gimpl, G., Wiegand, V., Burger, K., & Fahrenholz, F.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Gimpl, Gerald
- ORCID
- Gimpl, Gerald
- Venue
- Progress in brain research
- Publisher
- Elsevier
- Published
- 2002
- Volume
- 139
- Pages
- 43-55
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W1484250425
- Cited by
- 81
- References
- 68
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 3
- FWCI
- 1.43
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- oxytocin receptor, cholesterol, steroid hormones, progesterone, allosteric modulation, G protein-coupled receptor signaling, non-genomic signaling, cholesterol transport, receptor lateral mobility, receptor chimeras, uterine quiescence, filopodia, vesicle trafficking, post-transcriptional regulation
- MeSH terms
- Allosteric Regulation, Amino Acid Sequence, Animals, Cholesterol, Estrogens, Molecular Sequence Data, Progesterone, Protein Conformation, Signal Transduction, Receptors, Oxytocin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
