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.