Breast Cancer Research and Treatment

, Volume 92, Issue 1, pp 47–50 | Cite as

Long-term dysregulation of circadian and 17-β estradiol-induced LH, prolactinand corticosterone secretion after dimethylbenz (a) anthracene administrationin the Sprague–Dawley female rat

  • M. Beau Yon De Jonage-Canonico
  • V. Lenoir
  • R. Scholler
  • B. Kerdelhué


A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA) has been shown, when given at 55–60 days of age, to induce mammary tumors in young cycling female Sprague–Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances of the hypothalamo–pituitary–gonadal (HPG) axis, including attenuation of the preovulatory Luteinizing Hormone (LH) and Gonadotropin-Releasing Hormone (GnRH) release and amplification of the preovulatory 17β-Estradiol (E2) surge. In this study, we examined the hypothesis that a single administration of DMBA could also, in the long range, induce disturbances of others neuroendocrine axis, like the Hypothalamic–Pituitary–Adrenal (HPA) axis and/or the Lactotroph axis. Sprague–Dawley rats, 55–60 days of age, received, on the day of Estrous of the Estrous cycle, a single administration of 15 mg of DMBA delivered by intragastric intubation. Then, they were ovariectomized 5 days later. One month later, (1) Two groups of animal were sacrificed by decapitation at 09:00 a.m. and 05:00 p.m. to record the circadian rhythm of plasma LH, Prolactin (PRL) and corticosterone, (2) Three other groups of animal were sacrificed by decapitation at three different times after a morning subcutaneous administration of 50 μg/kg of Estradiol Benzoate (EB), to induce a negative and positive feed-back of the secretion of LH. Then, plasma LH, PRL and corticosterone concentrations were measured. After DMBA administration, (1) the negative–but not the positive-LH feed-back was seen, (2) the PRL circadian rhythm was blunted and the corticosterone circadian rhythm was almost absent, (3) the increase in PRL or Corticosterone plasma concentration was significantly reduced. In conclusion, a single administration of DMBA provokes a long-term dysregulation of not only the HPG axis but also of the lactotroph and HPA axis. These dysregulations, along with the already evidenced long-term inhibition of DMBA upon Melatonin secretion from the pineal gland, might accelerate the promotion of mammary tumors induced by the mammary carcinogen.


corticosterone DMBA female rat mammary cancer prolactin 


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Copyright information

© Springer 2005

Authors and Affiliations

  • M. Beau Yon De Jonage-Canonico
    • 1
  • V. Lenoir
    • 1
  • R. Scholler
    • 1
  • B. Kerdelhué
    • 1
  1. 1.Laboratoire de Neuroendocrinologie CNRS–FRE 2718UFR biomédicale, Université René DescartesCedex 06France

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