Journal of Comparative Physiology A

, Volume 193, Issue 4, pp 461–470 | Cite as

Endocrine modulation of a pheromone-responsive gene in the honey bee brain

Original Paper


Pheromones cause dramatic changes in behavior and physiology, and are critical for honey bee colony organization. Queen mandibular pheromone (QMP) regulates multiple behaviors in worker bees (Slessor et al. in J Chem Ecol 31(11):2731–2745, 2005). We also identified genes whose brain expression levels were altered by exposure to QMP (Grozinger et al. in Proc Natl Acad Sci USA 100(Suppl 2):14519–14525, 2003). Krüppel-homolog 1 (Kr-h1) RNA levels were significantly downregulated by QMP, and were higher in foragers than in nurses (Whitfield et al. in Science 302(5643):296–299, 2003). Here we report on results of behavioral and pharmacological experiments that characterize factors regulating expression of Kr-h1. Foragers have higher brain levels of Kr-h1 than in-hive bees, regardless of age and pheromone exposure. Furthermore, forager Kr-h1 levels were not affected by QMP. Since the onset of foraging is caused, in part, by increasing juvenile hormone blood titers and brain octopamine levels, we investigated the effects of octopamine and methoprene (a juvenile hormone analog) on Kr-h1 expression. Methoprene produced a marginal (not significant) increase in Kr-h1 expression, but Kr-h1 brain levels in methoprene-treated bees were no longer downregulated by QMP. Octopamine did not modulate Kr-h1 expression. Our results demonstrate that the gene expression response to QMP is not hard-wired in the brain but is instead dependent on worker behavioral state.


Apis mellifera Gene expression Juvenile hormone Queen mandibular pheromone Krüppel homolog 1 


  1. Amdam GV, Omholt SW (2003) The hive bee to forager transition in honeybee colonies: the double repressor hypothesis. J Theor Biol 223(4):451–464PubMedCrossRefGoogle Scholar
  2. Amdam GV, Aase AL, Seehuus SC, Kim Fondrk M, Norberg K et al (2005) Social reversal of immunosenescence in honey bee workers. Exp Gerontol 40(12):939–947PubMedCrossRefGoogle Scholar
  3. Anton S, Gadenne C (1999) Effect of juvenile hormone on the central nervous processing of sex pheromone in an insect. Proc Natl Acad Sci USA 96(10):5764–5767PubMedCrossRefGoogle Scholar
  4. Barron AB, Schulz DJ, Robinson GE (2002) Octopamine modulates responsiveness to foraging-related stimuli in honey bees (Apis mellifera). J Comp Physiol A Neuroethol Sens Neural Behav Physiol 188(8):603–610PubMedCrossRefGoogle Scholar
  5. Barron AB, Maleszka J, Vander Meer RK, Robinson GE, Maleszka R (2006) Comparing the efficiency of injection, feeding and topical application methods for pharmacological treatment of honey bees. J Ins Phys (in press)Google Scholar
  6. Beck Y, Pecasse F, Richards G (2004) Kruppel-homolog is essential for the coordination of regulatory gene hierarchies in early Drosophila development. Dev Biol 268(1):64–75PubMedCrossRefGoogle Scholar
  7. Ben-Shahar Y, Robinson GE (2001) Satiation differentially affects performance in a learning assay by nurse and forager honey bees. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 187(11):891–899PubMedCrossRefGoogle Scholar
  8. Ben-Shahar Y, Robichon A, Sokolowski MB, Robinson GE (2002) Influence of gene action across different time scales on behavior. Science 296(5568):741–744PubMedCrossRefGoogle Scholar
  9. Ben-Shahar Y, Leung HT, Pak WL, Sokolowski MB, Robinson GE (2003) cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of labor. J Exp Biol 206(Pt 14):2507–2515PubMedCrossRefGoogle Scholar
  10. Bloch G, Toma DP, Robinson GE (2001) Behavioral rhythmicity, age, division of labor and period expression in the honey bee brain. J Biol Rhythms 16(5):444–456PubMedCrossRefGoogle Scholar
  11. Bloch G, Sullivan JP, Robinson GE (2002) Juvenile hormone and circadian locomotor activity in the honey bee Apis mellifera. J Insect Physiol 48(12):1123–1131PubMedCrossRefGoogle Scholar
  12. Burns MJ, Nixon GJ, Foy CA, Harris N (2005) Standardisation of data from real-time quantitative PCR methods—evaluation of outliers and comparison of calibration curves. BMC Biotechnol 5:31PubMedCrossRefGoogle Scholar
  13. Dhadialla TS, Carlson GR, Le DP (1998) New insecticides with ecdysteroidal and juvenile hormone activity. Annu Rev Entomol 43:545–569PubMedCrossRefGoogle Scholar
  14. Fahrbach SE, Giray T, Farris SM, Robinson GE (1997) Expansion of the neuropil of the mushroom bodies in male honey bees is coincident with initiation of flight. Neurosci Lett 236(3):135–138PubMedCrossRefGoogle Scholar
  15. Grozinger CM, Pfischer P, Hampton JE (2007) Uncoupling primer and releaser responses to pheromone in the honey bee brain. Naturwissenschaften (in press)Google Scholar
  16. Grozinger CM, Sharabash NM, Whitfield CW, Robinson GE (2003) Pheromone-mediated gene expression in the honey bee brain. Proc Natl Acad Sci USA 100(Suppl 2):14519–14525PubMedCrossRefGoogle Scholar
  17. Grubbs FE, Beck G (1972) Extension of sample sizes and percentage points for significance tests of outlying observations. Technometerics 14(4):847–854CrossRefGoogle Scholar
  18. Hartfelder K, Bitondi MM, Santana WC, Simoes ZL (2002) Ecdysteroid titer and reproduction in queens and workers of the honey bee and of a stingless bee: loss of ecdysteroid function at increasing levels of sociality? Insect Biochem Mol Biol 32(2):211–216PubMedCrossRefGoogle Scholar
  19. Hoover SE, Keeling CI, Winston ML, Slessor KN (2003) The effect of queen pheromones on worker honey bee ovary development. Naturwissenschaften 90(10):477–480PubMedCrossRefGoogle Scholar
  20. Kaatz H-H, Hildebrandt H, Engels W (1992) Primer effect of queen pheromone on juvenile hormone biosynthesis in adult worker honey bees. J Comp Physiol [B](162):588–592Google Scholar
  21. Keverne EB (2005) Odor here, odor there: chemosensation and reproductive function. Nat Neurosci 8(12):1637–1638PubMedCrossRefGoogle Scholar
  22. Laidlaw J, H. H. (1987) Instrumental insemination of honeybee queens: its origin and development. Bee World 68:17–38Google Scholar
  23. McGovern VL, Pacak CA, Sewell ST, Turski ML, Seeger MA (2003) A targeted gain of function screen in the embryonic CNS of Drosophila. Mech Dev 120(10):1193–1207PubMedCrossRefGoogle Scholar
  24. Pankiw T, Huang Z, Winston ML, Robinson GE (1998) Queen mandibular gland pheromone influences worker honey bee (Apis mellifera L.) foraging ontogeny and juvenile hormone titers. J Insect Physiol 44(7–8):685–692PubMedCrossRefGoogle Scholar
  25. Pecasse F, Beck Y, Ruiz C, Richards G (2000) Kruppel-homolog, a stage-specific modulator of the prepupal ecdysone response, is essential for Drosophila metamorphosis. Dev Biol 221(1):53–67PubMedCrossRefGoogle Scholar
  26. Pham-Delegue MH, Trouiller J, Caillaud CM, Roger B, Masson C (1993) Effect of queen pheromone on worker bees of different ages: behavioral and electrophysiological responses. Apidologie 24:267–281Google Scholar
  27. Rachinsky A (1994) Octopamine and serotonin influence on corpora allata activity in honey bee (Apis mellifera) larvae. J Ins Phys 40(7):549–554CrossRefGoogle Scholar
  28. Robinson GE (1987) Modulation of alarm pheromone perception in the honey bee: evidence for division of labor based on homonally regulated response thresholds. J Comp Physiol 160:613–619CrossRefGoogle Scholar
  29. Robinson GE, Page RE Jr (1988) Genetic determination of guarding and undertaking in honey-bee colonies. Nature 333:356–358CrossRefGoogle Scholar
  30. Robinson GE, Ben-Shahar Y (2002) Social behavior and comparative genomics: new genes or new gene regulation? Genes Brain Behav 1(4):197–203PubMedCrossRefGoogle Scholar
  31. Robinson GE, Page RE Jr, Fondrk MK (1990) Intracolonial behavioral variation in worker oviposition, oophagy, and larval care in queenless honey bee colonies. Behav Ecol Sociobiol 26(5):315–323CrossRefGoogle Scholar
  32. Robinson GE, Grozinger CM, Whitfield CW (2005) Sociogenomics: social life in molecular terms. Nat Rev Genet 6(4):257–270PubMedCrossRefGoogle Scholar
  33. Robinson GE, Strambi C, Strambi A, Huang ZY (1992) Reproduction in worker honey bees is associated with low juvenile hormone titers and rates of biosynthesis. Gen Comp Endocrinol 87(3):471–480PubMedCrossRefGoogle Scholar
  34. Schulz DJ, Robinson GE (1999) Biogenic amines and division of labor in honey bee colonies: behaviorally related changes in the antennal lobes and age-related changes in the mushroom bodies. J Comp Physiol [A] 184(5):481–488CrossRefGoogle Scholar
  35. Schulz DJ, Sullivan JP, Robinson GE (2002) Juvenile hormone and octopamine in the regulation of division of labor in honey bee colonies. Horm Behav 42(2):222–231PubMedCrossRefGoogle Scholar
  36. Skals N, Anderson P, Kanneworff M, Lofstedt C, Surlykke A (2005) Her odours make him deaf: crossmodal modulation of olfaction and hearing in a male moth. J Exp Biol 208(Pt 4):595–601PubMedCrossRefGoogle Scholar
  37. Slessor KN, Winston ML, Le Conte Y (2005) Pheromone communication in the honeybee (Apis mellifera L.). J Chem Ecol 31(11):2731–2745PubMedCrossRefGoogle Scholar
  38. Slessor KN, Kaminski L-A, King GGS, Borden JH, Winston ML (1988) Semiochemical basis of the retinue response to queen honey bees. Nature 332:354–356CrossRefGoogle Scholar
  39. Toth AL, Kantarovich S, Meisel AF, Robinson GE (2005) Nutritional status influences socially regulated foraging ontogeny in honey bees. J Exp Biol 208(Pt 24):4641–4649PubMedCrossRefGoogle Scholar
  40. Whitfield CW, Cziko AM, Robinson GE (2003) Gene expression profiles in the brain predict behavior in individual honey bees. Science 302(5643):296–299PubMedCrossRefGoogle Scholar
  41. Whitfield CW, Ben-Shahar Y, Brillet C, Leoncini I, Crauser D et al (2006) Genomic dissection of behavioral maturation in the honey bee. Proc Natl Acad Sci USA 103(44):16068–16075PubMedCrossRefGoogle Scholar
  42. Winston ML (1987) The biology of the honey bee. Harvard University Press, Cambridge, p 281Google Scholar
  43. Wyatt TD (2003) Pheromones and animal behavior: communication by smell and taste. Cambridge University Press, Cambridge, p 408Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Departments of Entomology and Genetics, W.M. Keck Center for Behavioral BiologyNorth Carolina State UniversityRaleighUSA
  2. 2.Department of Entomology, Neuroscience Program, Institute for Genomic BiologyUniversity of IllinoisUrbana-ChampaignUSA

Personalised recommendations