Contact Information
Research Interests
Research Topics
Development, Endocrinology, Neurobiology
Disease Research Interests
Neurological and Behavioral Disorders, Reproductive Diseases, Infertility, and Menopause
Research Description
Notch signaling pathway in hypothalamic-pituitary gland development and disease
The pituitary is the master gland coordinating growth, fertility, metabolism and the body's response to stress. To exert these effects, the anterior pituitary has distinct cell types that produce thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). If the development or function of these cells in the pituitary gland is disrupted, two main diseases result. Hypopituitarism, defined as loss of at least one pituitary hormone, occurs in 1:4000 births. Only a small number of cases are caused by known genetic mutations. The other main category of pituitary disease, tumor formation, is very common, with an incidental prevalence of 30% at autopsy. The genetic causes of pituitary tumors are largely unknown and could result from the loss or gain of function of a normal developmental process.
Research in my laboratory is focused on understanding the role of cell-cell signaling during pituitary development. We hypothesize that the Notch signaling pathway may play an important role in the proliferation and lineage specific differentiation of progenitor cells in the embryonic pituitary. The Notch signaling pathway is an evolutionarily conserved mechanism that orchestrates cell fate choices in a broad spectrum of developmental systems. The core pathway includes two transmembrane ligands, (Delta and Jagged), a transmembrane receptor (Notch), a coactivator (CSL/Rbpsuh) and a downstream transcription factor (Hes). Many components of the Notch pathway are present in the developing pituitary, but their function in this system is unknown.
We are interested in uncovering the role of Notch signaling in the normal development of the pituitary and in pituitary disease. We are exploring if Notch signaling is necessary and sufficient for obtaining the full complement of cells in the pituitary by employing transgenic and knockout mice. These studies also take advantage of molecular genetic techniques and whole animal physiology.
Education
B.A. 1994 Ripon College, Ripon, WI
PhD. 2000 Case Western Reserve University, Cleveland, OH
Postdoc. 2000-2005 University of Michigan, Ann Arbor, MI
Awards and Honors
Medical Scholars Program Outstanding Advisor Award (2015)
James Heath Award for Excellence in Teaching (2010)
Additional Campus Affiliations
External Links
Highlighted Publications
Edwards WE, Nantie LB, and Raetzman LT. (2016). Identification of a novel progenitor marker, grainyhead like 2 in the developing pituitary. Dev. Dyn. 45, 1097-1106. [Abstract]
Eckstrum KS, Weis KE, Baur NG, Yoshihara Y, and Raetzman LT. (2016). Icam5 expression exhibits sex differences in the neonatal pituitary and is regulated by estradiol and bisphenol A. Endocrinol. 157, 1408-20. [Abstract]
Biehl MJ and Raetzman LT. (2015). Rbpj-κ mediated Notch signaling plays a critical role in development of hypothalamic Kisspeptin neurons Dev. Biol. 406:235-46. [Abstract]
Nantie LB, Himes AD, Getz DR, Raetzman LT. (2014). Notch signaling in postnatal pituitary expansion: proliferation, progenitors, and cell specification. Mol. Endocrinol.28(5):731-44. [Abstract]
Aujla PK, Naratadam GT, Xu L, Raetzman LT. (2013). Notch/Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons. Development 140(17):3511-21. [Abstract]
Moran TB, Brannick KE, Raetzman LT. (2012). Aryl-hydrocarbon receptor activity modulates prolactin expression in the pituitary. Toxicol. Appl. Pharmacol. 265(1):139-45. [Abstract]
Brannick KE, Craig ZR, Himes AD, Peretz JR, Wang W, Flaws JA, Raetzman LT. (2012). Prenatal exposure to low doses of bisphenol A increases pituitary proliferation and gonadotroph number in female mice offspring at birth. Biol. Reprod. 87(4):82. [Abstract]
Goldberg LB, Aujla PK, and Raetzman LT. (2011). Persistent Expression of Activated Notch Inhibits corticotrope and melanotrope differentiation and results in dysfunction of the HPA axis. Dev. Biol. 358:23-32. [Abstract]
Aujla P.K., Bora A., Monahan P., Sweedler J.V., and Raetzman L.T. (2011). The Notch effector gene Hes1 regulates migration of hypothalamic neurons, neuropeptide content and axon targeting to the pituitary. Dev. Biol. 353:61-71. [Abstract]
Recent Publications
Ge, X., Weis, K. E., & Raetzman, L. (2024). Glycoprotein hormone subunit alpha 2 (GPHA2): A pituitary stem cell-expressed gene associated with NOTCH2 signaling. Molecular and Cellular Endocrinology, 586, Article 112163. https://doi.org/10.1016/j.mce.2024.112163
Martinez-Mayer, J., Brinkmeier, M. L., O’Connell, S. P., Ukagwu, A., Marti, M. A., Miras, M., Forclaz, M. V., Benzrihen, M. G., Cheung, L. Y. M., Camper, S. A., Ellsworth, B. S., Raetzman, L. T., Pérez-Millán, M. I., & Davis, S. W. (2024). Knockout mice with pituitary malformations help identify human cases of hypopituitarism. Genome medicine, 16(1), Article 75. https://doi.org/10.1186/s13073-024-01347-y
Santacruz-Márquez, R., Safar, A. M., Laws, M. J., Meling, D. D., Liu, Z., Kumar, T. R., Nowak, R. A., Raetzman, L. T., & Flaws, J. A. (2024). The effects of short-term and long-term phthalate exposures on ovarian follicle growth dynamics and hormone levels in female mice. Biology of reproduction, 110(1), 196-208. Article ioad137. https://doi.org/10.1093/biolre/ioad137
Cutia, C. A., Leverton, L. K., Weis, K. E., Raetzman, L. T., & Christian-Hinman, C. A. (2023). Female-specific pituitary gonadotrope dysregulation in mice with chronic focal epilepsy. Experimental Neurology, 364, Article 114389. https://doi.org/10.1016/j.expneurol.2023.114389
De La Torre, K. M., Lee, Y., Safar, A., Laws, M. J., Meling, D. D., Thompson, L. M., Streifer, M., Weis, K. E., Raetzman, L. T., Gore, A. C., & Flaws, J. A. (2023). Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary. Reproductive Toxicology, 120, Article 108427. https://doi.org/10.1016/j.reprotox.2023.108427
