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| The Hammes laboratory is interested in a wide variety of subjects, ranging from signaling to enzymology to ovarian physiology. Our main focus has been the study of "nongenomic," or transcription-independent, steroid-mediated signaling. The list of rapid, steroid-triggered, nongenomic signals has grown rapidly in recent years, and includes estrogen-mediated activation of MAPK and Src in endothelial and breast cells, and vitamin D-induced signaling in osteoblasts. These steroid-induced signaling events may mediate important biological processes; however, in many cases, their physiologic relevance is still disputed. |
We have chosen to study nongenomic steroid signaling using the physiologically relevant phenomenon of steroid-induced maturation, or re-entry into meiosis, of frog oocytes. Using this system, we have 1) identified the physiologic steroids (androgens) that mediate frog oocyte maturation and completely mapped the steroidogenic pathway in the frog ovary; 2) characterized at least some of the steroid receptors mediating androgen-induced maturation; 3) begun characterization of the intracellular signals triggered by steroids, which include alterations in G protein-coupled events and cAMP production; and 4) examimined the kinetic parameters of the frog ovarian CYP17, a steroidogenic enzyme that is critical for androgen production but is expressed exclusively in oocytes in the frog ovary. |
In addition, we have begun studying maturation of mammalian oocytes, and have recently shown for the first time that androgens promote the same signals in mouse oocytes as in frogs. We have now started to examine mouse ovarain physiology in more detail, focusing on the role of androgens in normal ovarian development, as well as in ovarian pathology associated with states of androgen excess such as polycystic ovarian syndrome (PCOS). We have discovered selective androgen receptor modulators (SARMs) that specificallyi promote either genomic (transcriptional) or nongenomic AR-mediated signaling, and hope to use these both in our studies and perhaps clinically.
In summary, our laboratory's focus is on the role of steroids in mediating oocyte maturation and ovarian development in all animals. |
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