Medullary Thyroid Carcinoma Arises in the Absence of Prolactin Signaling-

Authors
C. Kedzia, L. Lacroix, N. Ameur, T. Ragot, P. A. Kelly et al.

Lab
Faculté de Médecine Necker, Institut National de la Sante et de la Recherche Medicale U584, Hormone Targets, Paris, France.

Journal
Cancer Research

Abstract
Prolactin, a pituitary hormone, exerts pleiotropic effects in various cells. These effects are mediated by a membrane receptor highly expressed in many tissues. To analyze prolactin effects on the thyroid gland, we first identified prolactin receptor (PRLR) mRNAs by in situ hybridization. To further evaluate the physiologic relevance of PRLR actions in the thyroid in vivo, we used PRLR knockout mice. Whereas the histologic structure of thyroid of PRLR- mice was not disturbed, we show that T4 levels are lower in animals (13.63 ± 2.98 versus 10.78 ± 2.25 pmol/L in mice), confirming that prolactin participates in the control of thyroid metabolism. To further investigate thyroid effects in mice, we measured body temperature and thyroid-stimulating hormone in young and adult male and/or female PRLR- mice and their normal siblings. Surprisingly, in animals, we saw medullary thyroid carcinoma (MTC) arising from parafollicular C cells producing calcitonin. The incidence of these carcinomas attained 41% in PRLR- mice, whereas this malignant tumor occurs sporadically or as a component of the familial cancer syndrome in humans. This finding suggests that PRLR- mice could represent a valuable animal model for MTC, which could be compared with existing MTC models. These observations suggest a possible link between the appearance of this carcinoma and the absence of prolactin signaling.