פרופ' צבי נאור

We are interested mainly in signaling of GnRHR, a model G-protein coupled receptors (GPCRs), which is the key hormone of reproduction. The mechanism of action of GnRH upon gonadotropin (LH and FSH) release and gene expression is not fully understood. In addition, chronic administration of GnRH analogs desensitizes the pituitary gonadotropes, inducing “Chemical castration” and is the first choice for treatment of prostate cancer. Since GnRH analogs exert also a direct apoptotic effect on human prostate cancer cell lines, we are trying to develop a novel GnRH analog based therapy using the principal of “Killing the messenger” for advanced human prostate cancer for which there is no cure to date.

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For a full list of publications

Since 2009 

Naor, Z. Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor. Frontiers in Neuroendocrinology 30: 10-29 (2009).

Dobkin-Bekman, M., Naidich, M., Rahamim, L., Przedecki, F., Almog, T., Lim, S., Melamed, P., Liu, P., Wohland, T., Yao, Z., Seger, R, and Naor, Z. A Pre-formed Signaling Complex Mediates GnRH-Activated ERK-Phosphorylation of Paxillin and FAK at Focal Adhesions in LbetaT2 Gonadotrope Cells. Mol Endo 23: 1850-1864 (2009).

Lim, S., Pnueli, L., Tan, J.H., Naor Z., Rajagopal, G. and Melamed, P. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency. PLOS one 4:e7244 (2009).

Dobkin-Bekman, M., Ben-Navi, L. R., Shterntal, B., Sviridonov, L., Przedecki, F., Naidich-Exler, M., Brodie, C., Seger, R, and Naor, Z. Differential Role of PKC Isoforms in GnRH and phorbol 12-myristate 13-acetate Activation of Extracellular Signal-Regulated Kinase and Jun N-Terminal Kinase. Endocrinology 151: 4894-4907 (2010).

Almog, T. and Naor, Z. The role of Mitogen activated protein kinase (MAPK) in sperm functions. Mol Cell Endocrinol 314:239-43 (2010).

Naidich, M., Shterntal, B., Furman, R., Pawson, A., Jabbour, H.N., Morgan, K., Millar, R.P., Jia, J., Tomic, M., Stojilkovic, S., Stern, N, and Naor, Z. Elucidation of Mechanisms of the Reciprocal Cross-talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors. Endocrinology 151: 2700-2712 (2010).

Ben-Ami,I., Yao,Z., Naor, Z., Seger, R. Gq Protein-induced Apoptosis Is Mediated by AKT Kinase Inhibition That Leads to Protein Kinase C-induced c-Jun N-terminal Kinase Activation. J Biol Chem. 286:31022-31 (2011).

Kauschansky A, Orvieto R, Yeshaya A, Shterntal B, Naor Z.Insight: Prolonged Vaginal Bleeding during Central Precocious Puberty Therapy with a Long-acting Gonadotropin-Releasing Hormone Agonist: A Proposed Mechanism and Management Plan.J Pediatr Adolesc Gynecol 24: 365-367 (2011).

Sviridonov, L., Dobkin-Bekman, M., Shterntal, B., Przedecki, F., Formishell, L., Kravchook, S., Rahamim-Ben Navi, L., Bar-Lev, TH., Kazanietz, M., Yao, Z., Seger, R., and Naor, Z. Differential signaling of the GnRH receptor in pituitary gonadotropes and prostate cancer cells Mol Cell Endocrinology 369: 107-118 (2013).

Naor, Z. and Huhtaniemi, I. Interactions of the GnRH receptor with heterotrimeric G proteins.  Frontiers in Neuroendocrinology 34: 88-94 (2013).

Bar-Lev, T., Harris, D., Tomić, M.,  Stojilkovic, S., Blumenfeld, Z., Brown, P., Seger, R., and Naor, Z. Role of PI4K and PI3K-AKT in  ERK1/2 activation by GnRH in the Pituitary Gonadotropes. Mol Cell Endocrinology 415: 12-23 (2015).

Rahamim Ben Navi, L., Almog, T., Yao,Z., Seger,R. and Naor, Z A-Kinase Anchoring Protein 4 (AKAP4) is an ERK1/2 substrate and a switch molecule between cAMP/PKA and PKC/ERK1/2 in human spermatozoa. Sci Rep. 2016, 6:37922. doi: 10.1038/srep37922.

Mugami, S., Kravchook, S., Rahamim–Ben Navi, L., Seger, R., and Naor, Z. Differential Roles of  PKC Isoforms (PKCs) and Ca2+ in GnRH and Phorbol  12-myristate 13-acetate (PMA) Stimulation of  p38MAPK Phosphorylation in Immortalized Gonadotrope Cells. Mol Cell Endocrinol 439: 141-         154 (2017).

Mugami, S., Dobkin-Beckman, M.,Rahamim–Ben Navi, L. and Naor, Z. Differential Roles of  PKC Isoforms (PKCs) in GnRH Stimulation of  MAPK Phosphorylation in gonadotrope-derived cells. Mol Cell Endocrinol . DOI: 10.1016/j.mce.2017.04.004

Rahamim Ben Navi, L., Tsukerman, A., Feldman, A., Melamed, P., Tomić, M., Stojilkovic, S.S., Boehm, U., Seger, R. and Naor, Z. GnRH induces ERK-dependent bleb formation in gonadotrope cells, involving recruitment of members of a GnRH receptor-associated signalosome to the blebs Front. Endocrinol  8:113. doi: 10.3389/fendo.2017.00113.