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Life Science III, Room 2070
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- PHSL 430/530 Molecular and Cellular Physiology
- Medical Physiology Resource Sessions in the Endocrinology, Reproduction and GI unit
- Medical School Year One Problem Based Learning Tutor (ERG unit)
The luteinizing hormone chorionic gonadotropin receptor (LHCGR) and follicle stimulating hormone receptor (FSHR) are G protein-coupled receptors critical for mammalian reproduction. Loss-of-function and gain-of-function mutations result in developmental and reproductive defects such as male psuedohermaphroditism, hypospadias, Leydig cell hypoplasia, infertility, ovarian hyperstimulation syndrome, male-limited precocious puberty (FMPP), Leydig cell hyperplasia and tumors.
We have developed a mouse model of FMPP caused by a gain-of-function mutation in LHCGR. These mice exhibit precocious puberty, progressive infertility and develop Leydig cell adenomas. Current research in my laboratory is focused on understanding the mechanisms by which gain-of-function mutations in LHR cause progressive infertility and the long-term effects of sustained high steroid hormone levels on male and female reproduction.
Meehan, T.P., Puett, D. and Narayan, P. (2004) Tightly regulated and inducible expression of a yoked hormone-receptor complex in HEK 293 cells. J. Mol. Endocrinol. 32: 247-255. PMID:14766006
Angelova, K., Fremont, V., Jain, R., Zhang, M., Puett, D., Narayan, P. and Szkudlinski, M.W. (2004) Human a-subunit analogs act as partial agonists to the thyroid stimulating hormone receptor: Differential effects of free and yoked subunits. Endocrine 24: 25-32. PMID:15249700
Meehan, T.P., Harmon, B.G., Overcast, M.E., Yu, K.K., Camper, S.A., Puett, D. and Narayan, P. (2005) Gonadal defects and hormonal alterations in transgenic mice expressing a single chain human chorionic gonadotropin-lutropin receptor complex. J. Mol. Endocrinol 34:489-503. PMID:15821112
Puett, D., Li, Y., Angelova, K., DeMars, D., Meehan, T.P., Fanelli, F. and Narayan, P. (2005) Structure-Function Relationships of the Luteinizing Hormone Receptor. Annals of the NY Academy of Sciences 1061:41-54. PMID:16467256
Meehan, T.P. and Narayan, P. (2007) Constitutively active luteinizing hormone receptors: consequences of in vivo expression. Mol. Cell. Endocrinol. 260-262:294-300. PMID:17045736
Coonce, M.M., Rabideau, A.C., McGee, S., Smith, K. and Narayan P. (2009) Impact of a constitutively active luteinizing hormone receptor on testicular gene expression and postnatal Leydig cell development. Mol. Cell. Endocrinol. 298:33-41. PMID:19013498
Shirley, M.L., Venable, A., Rao, R.R., Boyd, N.L., Stice, S.L., Puett, D. and Narayan, P. (2012) Bone morphogenetic protein-4 affects both trophoblast and non-trophoblast lineage-associated gene expression in human embryonic stem cells. Stem Cell Discovery 2:163-175.
Ascoli M.A. and Narayan, P. (2013) The Gonadotropin Hormones and their Receptors in Yen and Jaffe’s Reproductive Endocrinology, 7th Edition, Eds. Strauss, J.L. and Barbieri, R.L., Elsevier, Philadelphia, PA. pp. 27-44.
McGee, S.R. and Narayan, P. (2013) Precocious puberty and Leydig cell hyperplasia in male mice witha gain of function mutation in the LH receptor gene. Endocrinology 154: 3900-3913. PMID:23861372
Jasurda JS, Jung DO, Froeter ED, Schwartz DB, Hopkins TD, Farris CL, McGee S, Narayan P, Ellsworth BS. (2014) The forkhead transcription factor, FOXP3: a critical role in male fertility in mice. Biol. Reprod. 90:4,1-8. PMID 24258212
Hai, L, McGee, S.R., Rabideau, A.C., Paquet, M. and Narayan, P. (2015) Infertility in Female Mice with a Gain-of-Function Mutation in the Luteinizing Hormone Receptor is due to Irregular Estrous Cyclicity, Anovulation, Hormonal Alterations and Polycystic Ovaries. Biol. Reprod. 93:16, 1-11. PMID 26040673.
Narayan, P. (2015) Genetic models for the study of luteinizing hormone receptor function. Front. Endocrinol. 6: 152.
Hai, L., Hiremath, D.S., Paquet, M. and Narayan, P. (2017) Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice. Biol. Reprod. 96:1007-1018.