Recent studies have highlighted the importance of Patient-Oriented Research, drawing attention to the relatively small number of investigators trained to conduct high-quality clinical research. There are a number of key points at which appropriate and committed mentoring is critical for attracting talented individuals to clinical investigation and providing them with quality training and career guidance: 1) at the premedical and medical school level; 2) during specialty and subspecialty training; and 3) during the transition from Fellow to independent investigator. Mechanisms have been established within the applicant's Unit and Institution and are being put in place within the Partner's Healthcare System and Harvard Medical School to recruit and provide the environment for training of such individuals. However, the success of each of these initiatives is critically dependent on the availability of qualified investigators who can teach by example and are committed and able to invest in mentoring the next generation. There is a particular need for rigorous and innovative patient-oriented investigation in the areas of reproductive health in women. This grant provides the mechanism for supporting the mentoring activities of the applicant while ensuring that her own patient-oriented research efforts are not compromised. The broad goal of the research plan is to continue to examine the neuroendocrine and gonadal regulation of reproduction in the female, focusing on the critical control of FSH secretion. Understanding the relative contributions of inhibins A and B to the control of FSH secretion during the normal menstrual cycle and defining the relationships of the inhibins and activin to GnRH and sex steroids are critical preludes to any precise definition of discrete pathophysiologic reproductive endocrine defects and the subsequent establishment of rational treatments. This research plan reflects the longstanding research interest of the PI in reproductive endocrinology, and more importantly, in the need to understand the normal physiology of reproduction as a critical step in unraveling the pathophysiologic processes underlying reproductive disorders and designing rational therapeutic approaches. This research plan is particularly relevant to the overall mentoring goals of the Midcareer Investigator Award in Patient-Oriented Research as it uses a variety of investigational models to address its goals and actively demonstrates a number of the key liaisons which are critical to translational research, combining studies of human physiology and pathophysiology with basic science and animal studies with outcomes research approaches which provide a rigorous evaluation of direct therapeutic implications.
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