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Brief description of current research:
Our laboratory studies the LH and FSH receptors, G protein-coupled receptors expressed primarily in ovaries and testes, in the context of elucidating their mechanisms of action and their roles in reproductive endocrinology. In recent years, we have determined that LH and/or FSH receptor are surprisingly expressed in several extra-gonadal tissues and we are actively pursuing the physiological roles of the receptors in these unique contexts. Of particular relevance to the Diabetes Research Center is our finding that LH and FSH receptors are present on human and mouse adipocytes. Studies using mouse 3T3-L1 adipocytes indicate that LH and FSH each stimulate the secretion of leptin, and preliminary in vivo studies in mice suggest complex roles for LH and FSH, independent of gonadal steroid hormone biosynthesis, in regulating energy homeostasis. Ongoing experiments are aimed at clarifying the actions of LH and FSH on adipocytes and on integrated energy homeostasis and elucidating the mechanisms underlying these unique hormonal effects.
3 most influential diabetes/obesity/metabolism publications:
- Guan, R., Feng, X., Wu, X., Zhang, M., Zhang, X., Hébert, T.E., and Segaloff, D.L. Bioluminescence resonance energy transfer studies reveal constitutive dimerization of the human lutropin receptor and a lack of correlation between receptor activation and the propensity for dimerization. J. Biol. Chem., 284:7483-7494:2009.
- Newton, C.L., Whay, A.M., van Koppen, C.J., van de Lagemaat, R., McCardle, C.A., Zhang, M., Segaloff, D.L., and Millar, R.P. Rescue of expression and signaling of human luteinizing hormone G protein coupled-receptor mutants with an allosterically binding small-molecule agonist. Proc. Natl. Acad. Sci., 108: 7172-7176, 2011.
- Feng, X., Zhang, M., Guan, R., and Segaloff, D.L. Heterodimerization between the lutropin and follitropin receptors is associated with an attenuation of hormone-dependent signaling. Endocrinology, 154:3925-3930, 2013.