Deborah L. Segaloff, Ph.D.
        Professor

Office: Lab: Phone: Lab: FAX: Email:

5-470 Bowen Science Building 5-471 Bowen Science Building (319) 335-7850 (319) 335-7832 (319) 335-7330 deborah-segaloff@uiowa.edu

Research Interests

G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors, regulating a wide array of physiological processes. My laboratory is interested in the mechanism of action of GPCRs, in particular the LH and FSH receptors (gonadotropin receptors), which play a pivotal role in reproductive endocrinology. The gonadotropin receptors, as well as the structurally related TSH receptor, are composed of a 7TM region that shares homology with the rhodopsin family of GPCRs as well as a large extracellular domain. The binding of hormone to the extracellular domain of the LH, FSH, or TSH receptor or the introduction of constitutively activating mutations stabilize the receptor in an active state such that the 7TM region can then activate G proteins (primarily Gs). We are exploiting differences in the functional activities of the LH, FSH, and TSH receptors (basal, mutation-induced, and hormone-stimulated) to identify the structural features of the receptors that mark their resting versus active states.

In related studies, using a variety of experimental approaches including resonance energy transfer techniques, we have shown that the LH and FSH receptors constitutively associate to form homodimers and, when co-expressed, heterodimers. We are currently studying the functional ramifications of these phenomena. In addition, studies are directed towards elucidating the mechanisms of hormone binding and G protein activation in the context of a gonadotropin receptor dimer.

Selected Publications

1. Freitas, K.C.M., Ryan, G., Brito, V.N., Tao, Y.-X., Mendonca, B.B., Segaloff, D.L., and Latronico, A.C. Molecular analysis of the neuropeptide Y1 receptor gene (NPY-Y1R) in human idiopathic gonadotropin-dependent precocious puberty and isolated hypogonadotropic hypogonadism. Fert. Steril., 87:627-634, 2007.

2. *Ryan, G.L., Feng, X., d’Alva, C.B., Zhang, M., Van Voorhis, B.J., Pinto, E.M., Kubias, A.E.F., Antonini, S.R., Latronico, A.C., and Segaloff, D.L. Evaluating the roles of follicle-stimulating hormone receptor polymorphisms in gonadal hyperstimulation associated with severe juvenile hypothyroidism. J. Clin. Endocrinol. Metabol., 92:2312-2317, 2007.
*Selected by the Faculty of 1000 Medicine

3. Zhang, M., Tao, Y.-X., Ryan, G.L., Fang, X., Fanelli, F., and Segaloff, D.L. Intrinsic differences in the response of the human lutropin receptor versus the human follitropin receptor to activating mutations, J. Biol. Chem., 282:25527-25539, 2007.

4. Feng, X., Muller, T., Mizrachi, D., Fanelli, F., and Segaloff, D.L. An intracellular loop 2 (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and Helix 6, via Helix 3. Endocrinology, 149:1705-1717, 2008.