This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wysolmerski, J. J. Articles by Silve, C. Search for Related Content PubMed PubMed Citation Articles by Wysolmerski, J. J. Articles by Silve, C.

Absence of Functional Type 1 Parathyroid Hormone (PTH)/PTH-Related Protein Receptors in Humans Is Associated with Abnormal Breast Development and Tooth Impaction¹

Division of Endocrinology and Metabolism (J.J.W., W.M.P., P.D., J.-P.Z.), Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020; INSERM U-426 et Institut Fédératif de Recherche 02 (S.C., C.S.), Faculté de Médecine Xavier Bichat, 75018, Paris, France; Service d’Histo-Embryologie et Cytogénétique (J.R.), Hôpital Saint Antoine, Debré AP-HP, 75012, Paris, France; and Service de Biologie du Développement (A.-L.D.), Hôpital Robert Debré, 75935 Paris Cedex 19, France

Address all correspondence and requests for reprints to: Caroline Silve, M.D., Ph.D., INSERM U-426 et Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France. E-mail: silve{at}bichat.inserm.fr

Recent studies in transgenic mice have demonstrated that PTH-related protein (PTHrP), signaling through the type 1 PTH/PTHrP receptor (PTHR1), regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Recently, it has been shown that loss-of-function mutations in the PTHR1 gene result in a rare, lethal form of dwarfism known as Blomstrand chondrodysplasia. These patients suffer from severe defects in endochondral bone formation, but abnormalities in breast and tooth development have not been reported. To ascertain whether PTHrP signaling was important to human breast and tooth development, we studied two fetuses with Blomstrand chondrodysplasia. These fetuses lack nipples and breasts. Developing teeth were present, but they were severely impacted within the surrounding alveolar bone, leading to distortions in their architecture and orientation. Compatible with the involvement of PTHR1 and PTHrP in human breast and tooth morphogenesis, both were expressed within the developing breasts and teeth of normal human fetuses. Therefore, impairment of the PTHrP/PTHR1 signaling pathway in humans is associated with severe abnormalities in tooth and breast development. In addition to regulating human bone formation, this signaling pathway is also necessary for the normal development of the human breast and tooth.

This article has been cited by other articles:

				D. Miao, H. Su, B. He, J. Gao, Q. Xia, M. Zhu, Z. Gu, D. Goltzman, and A. C. Karaplis Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein PNAS, December 23, 2008; 105(51): 20309 - 20314. [Abstract] [Full Text] [PDF]

				J. R. Hens, P. Dann, J.-P. Zhang, S. Harris, G. W. Robinson, and J. Wysolmerski BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction Development, March 15, 2007; 134(6): 1221 - 1230. [Abstract] [Full Text] [PDF]

				J. Hoogendam, H. Farih-Sips, L. C. Wynaendts, C. W. G. M. Lowik, J. M. Wit, and M. Karperien Novel Mutations in the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Type 1 Causing Blomstrand Osteochondrodysplasia Types I and II J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1088 - 1095. [Abstract] [Full Text] [PDF]

				A. Kato, M. Suzuki, Y. Karasawa, T. Sugimoto, and K. Doi PTHrP and PTH/PTHrP Receptor 1 Expression in Odontogenic Cells of Normal and HHM Model Rat Incisors Toxicol Pathol, June 1, 2005; 33(4): 456 - 464. [Abstract] [Full Text] [PDF]

				T. Thyagarajan, S. Totey, M. J. S. Danton, and A. B. Kulkarni GENETICALLY ALTERED MOUSE MODELS: THE GOOD, THE BAD, AND THE UGLY Critical Reviews in Oral Biology & Medicine, May 1, 2003; 14(3): 154 - 174. [Abstract] [Full Text] [PDF]

				S. Cormier, A.-L. Delezoide, C. Benoist-Lasselin, L. Legeai-Mallet, J. Bonaventure, and C. Silve Parathyroid Hormone Receptor Type 1/Indian Hedgehog Expression Is Preserved in the Growth Plate of Human Fetuses Affected with Fibroblast Growth Factor Receptor Type 3 Activating Mutations Am. J. Pathol., October 1, 2002; 161(4): 1325 - 1335. [Abstract] [Full Text] [PDF]

				T. J. Martin and M. T. Gillespie Editorial: Of Mice and Men, Recapitulation of Blomstrand's Chondrodysplasia J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1487 - 1488. [Full Text]