John C. Marshall, MD, PhD
Mechanisms of GnRH regulation of gonadotropin and steriod synthesis; role of follistatin and activin in modulating SMAD activity and cellular function
The work within the Marshall laboratory involves the study of cellular physiology and pathophysiology with direct application to cancer cell biology. One aspect of their research endeavor relates to the study of GnRH (Gonadotropin Releasing Hormone) action via the GnRH receptor. They are closely studying the means by which GnRH alters gonadotrope cell responses to a variety of additional reproductive stimuli, including subsequent GnRH exposure itself. The dynamic regulation of GnRH receptor expression is an integral part of reproduction and the phenomenon of receptor down-regulation has been utilized in the management of patients with prostate cancer and is more recently for gynecological cancer. The basis for administration of long-acting GnRH analogs is to induce receptor desensitization and thereby prevent gonadotrope signals to the gonads and thus reduce androgen production. The interplay between hypothalamic GnRH, gonadal peptide and gonadal steroid levels likely determines gonadotrope responsivity, and may play a role in extrapituitary sites as well. They are also currently studying the means whereby the gonadal peptide activin activates the SMADs and thereby generates nuclear activation of activin responsive genes. In this regard, it is highly likely that their work will have relevance in other cell systems where activin and TGF beta regulate cell growth such as in human prostate cancer and breast cancer.