Tumor Biology

, Volume 32, Issue 3, pp 543–549 | Cite as

Hypothalamus–pituitary–thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system

  • María Pilar Carrera-González
  • María Jesús Ramírez-Expósito
  • Jose Manuel Arias de Saavedra
  • Rafael Sánchez-Agesta
  • María Dolores Mayas
  • Jose Manuel Martínez-Martos
Research Article

Abstract

Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-β-naphthylamide as the substrate, in the hypothalamus–pituitary–thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

Keywords

N-Methyl nitrosourea Thyroid-stimulating hormone Free thyroxine Oxytocin Oxytocinase Thyroid Breast cancer 

Notes

Acknowledgments

This work was supported by Junta de Andalucía through PAI BIO-296, Universidad de Jaén (grant number UJA2003/014), and Instituto de Estudios Giennenses (IEG; grant number 135/24102006).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • María Pilar Carrera-González
    • 1
  • María Jesús Ramírez-Expósito
    • 1
  • Jose Manuel Arias de Saavedra
    • 2
  • Rafael Sánchez-Agesta
    • 2
  • María Dolores Mayas
    • 1
  • Jose Manuel Martínez-Martos
    • 1
  1. 1.Experimental and Clinical Physiopathology Research Group, Department of Health Sciences, Faculty of Experimental and Health SciencesUniversity of JaénJaénSpain
  2. 2.Complejo Hospitalario de JaénJaénSpain

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