Our laboratory has two main interests: Nongenomic steroid-mediated signaling and ovarian physiology.
First, we are interested in studying how steroid hormones mediate "nongenomic", or transcription-independent, effects. The growing list of rapid, steroid-triggered, nongenomic signaling events includes estrogen-mediated upregulation of nitric oxide synthase (NOS) in endothelial cells, vitamin D-induced increases in intracellular calcium in osteosarcoma cells, and steroid-induced maturation of frog and fish oocytes. These steroid-induced signaling events may mediate important biological processes such as blood vessel relaxation, bone metabolism, and fertilization. We have chosen to use the phenomenon of androgen-induced maturation, or re-entry into meiosis, of oocytes as a system to further characterize the role of membranes and membrane proteins in mediating nongenomic steroid responses. We have used frog oocyte systems to define the physiologic steroids and steroid receptors that mediate maturation. In addition, we are studying the signaling pathways triggered by steroids, and have identified G proteins and novel steroid receptor binding scaffold proteins that are involved in steroid-mediated oocyte maturation.
Our second focus is to study the roles of steroids in mediating mammalian follicle and oocyte development. We have shown that, similar to frogs, both androgens and estrogens can promote mouse oocyte maturation in vitro in a nongenomic fashion that may involve their classical receptors. Since oocytes are known to interact with surrounding follicle cells to regulate follicle development, we believe that physiologic levels of androgens might be important for normal ovarian development. In contrast, supraphysiologic concentrations might be promoting ovarian pathology, as seen in diseases of androgen excess such as polycystic ovarian disease (PCOS). Notably PCOS affects millions of young women throughout the world, and is the leading cause of infertility in reproductive age women. We have developed selective androgen receptor modulators (SARMs) that specifically mediate nongenomic versus genomic signaling, and hope to use them as reagents to control the abnormal follicular growth in these individuals with androgen excess. In addition, we have uncovered novel signaling pathways that regulate ovarian steroid production, and hope to block these signals to regulate ovarian steroid production both in normal women and, more importantly, those with PCOS.
We hope that our studies will lead to a better understanding of how steroids can signal independent of transcription. Further, we hope that our work will further elucidate the critical role of androgens in ovarian development and pathology.
RESEARCH INTERESTS
Ovarian physiology and development
Androgen-mediated signaling
Steroid metabolism
Reproduction and Reproductive Biology
G proteins and G protein-coupled receptors
RECENT PUBLICATIONS
Gill, A., Jamnongjit, M., and Hammes, S.R., "Androgens promote maturation and signaling in mouse oocytes independent of transcription: a release of inhibition model for mammalian oocyte meiosis" Molecular Endocrinology, 18:97-104, January 2004
Haas, D., White, S.N., Lutz, L.B., Rasar, M., and Hammes, S.R., "The Modulator of Nongenomic Actions of the Estrogen Receptor (MNAR) Regulates Transcription-Independent Androgen Receptor-Mediated Signaling: Evidence that MNAR Participates in G Protein-Regulated Meiosis in Xenopus leavis Oocytes" Molecular Endocrinology, 19:2035-2046, August 2005
Jamnongjit, M., Gill, A., and Hammes, S.R., "Epidermal Growth Factor Signaling is Required for Normal Ovarian Steroidogenesis and Oocyte Maturation" Proc. Natl. Acad. Sci. USA, 102:16257-16261, Fall 2005
Rasar, M. DeFranco, D.B., and Hammes, S.R., "Paxillin Regulates Steroid-Triggered Meiotic Resumption in Oocytes by Enhancing an All-or-None Positive Feedback Kinase Loop" Journal of Biological Chemistry, 281:39455-64, Fall 2006
Evaul, K., Jamnongjit, M., Bhagavath, B., and Hammes, S.R., "Androgens Rapidly Attenuate Plasma Membrane G??-Mediated Signaling in Xenopus Laevis Oocytes" Molecular Endocrinology, 21:186-96, Winter 2007
SIGNIFICANT PUBLICATIONS
Lutz, L.B., Kim, B.E., Jahani, D., and Hammes, S.R., "G Protein bg Subunits inhibit Nongenomic Progesterone-Induced Signaling and Maturation in Xenopus Laevis Oocytes: Evidence for a Release of Inhibition Mechanism for Cell Cycle Progression" Journal of Biological Chemistry, 275:41512-41520, 2000
Lutz, L.B., Cole, L.M., Gupta, M.K., Kwist, K.W., Auchus, R.J., Hammes, S.R., "Evidence that Androgens are the Primary Steroids Produced by Xenopus laevis Ovaries and may Signal Through the Classical Androgen Receptor to Promote Oocyte Maturation" Proc. Natl.Acad.Sci. USA, 98:13728-33, 2001
Hammes, S.R., "Steroids and Oocyte Maturation - A New Look at an Old Story" Molecular Endocrinology, 18:769-75, Spring 2004
Haas, D., White, S.N., Lutz, L.L., Rasar, M., and Hammes, S.R., "The Modulator of Nongenomic Actions of the Estrogen Receptor (MNAR) Regulates Transcription-Independent Androgen Receptor-Mediated Signaling: Evidence that MNAR Participates in G Protein-Regulated Meiosis of Xenopus Laevis Oocytes" Molecular Endocrinology, 19:2035-2046, August 2005
Jamnongjit, M., Gill, A., and Hammes, S.R., "Epidermal Growth Factor Signaling is Required for Normal Ovarian Steroidogenesis and Oocyte Maturation" Proc. Natl. Acad. Sci. USA, 102:16257-16261, 2005
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