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Our laboratories major interests are
1) the mechanisms by which neural peptides from the hypothalamus are released in varying pulse patterns and regulate transcription of the pituitary hormones which control metabolism (TSH) and reproduction (LH);
2) mechanisms of estrogen receptor action.
In the first area, we have identified the regions of the pituitary hormone genes which confer hypothalmic regulation, and some of the protein transcription factors which mediate this response. Importantly, we have determined that the LHa and LHb subunit genes, which are regulated physiologically by different pulse frequencies of hypothalamic GnRH, are controlled by different arms of the GnRH intracellular signaling pathways. This appears to be reflected in divergent gene targets for the GnRH signal, and we are working to identify the critical proteins responsible for these timed events in reproduction and development.
In our second area of research, we have found specific isoforms of the estrogen receptor (ER), which mediates the biological effects of the hormone estrogen. We have cloned tissue-specific forms of the ER, including some with unique biological functions. One of these TERP, is found specifically in female pituitary tissue, is highly regulated by estrogen and through the reproductive cycle, and appears to modify or controls the activity of the other ER forms. We are investigating TERP mechanism of action. We are also testing the hypothesis that growth factors act on specific isoforms of ER in human breast cancer, and are part of the process of development of hormone-independent breast cancers.
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Shupnik MA (1996) Gonadotropin gene modulation by steroids and gonadotropin-releasing hormone. Biol Reprod 1996 54(2):279-286. |
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Friend KE, Resnick EM, Ang LW, Shupnik MA (1997) Specific modulation of estrogen receptor mRNA isoforms in rat pituitary throughout the estrous cycle and in response to steroid hormones. Mol Cell Endocrinol 131(2):147-155. |
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Weck J, Fallest PC, Pitt LK, Shupnik MA (1998) Differential gonadotropin-releasing hormone stimulation of rat luteinizing hormone subunit gene transcription by calcium influx and mitogen-activated protein kinase-signaling pathways. Mol Endocrinol 12(3):451-457. |
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Shupnik MA, Pitt LK, Soh AY, Anderson A, Lopes MB, Laws ER Jr (1998) Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J Clin Endocrinol Metab 83(11):3965-3972 |
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Schreihofer DA, Resnick EM, Soh AY, Shupnik MA (1998) Transcriptional regulation by a naturally occurring truncated rat estrogen receptor (ER), truncated ER product-1 (TERP-1). Mol Endocrinol 13(2):320-329 |
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Resnick EM, Schreihofer DA, Periasamy A, Shupnik MA (2000) Truncated Estrogen Receptor Product-1 Suppresses Estrogen Receptor Transactivation by Dimerization with Estrogen Receptors alpha and beta. J Biol Chem 275(10):7158-7166 |