ROLE OF STRESS IN PCOS: NEURONAL MECHANISMS

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Polycystic Ovarian Syndrome (PCOS), the leading cause of infertility in women, is characterized by arrested growth of antral follicles by currently unknown mechanisms. Recent evidence in primate ovaries suggests a role for catecholamines, specifically norepinephrine, also known as a stress hormone, as regulators of follicular growth. The increased density of nerve fibers that release catecholamines observed in PCOS ovaries, as well as evidence for altered levels of catecholamines in follicular fluid from PCOS follicles;provide the rationale to explore these factors in a more direct approach. Importantly, the cellular mechanism responsible for up-take, storage and release of catecholamines are found in both human and monkey follicles, thus creating a follicular microenvironment that could regulate follicular function. In order to directly address the question whether and how catecholamines can impact follicular growth and function, we are using the novel technique of 3-dimensional culture of follicles recently developed in the macaque. Primary and secondary follicles are isolated from macaque ovaries, encapsulated in an alginate matrix and individually cultured with natural catecholamines and drugs which are able to interfere with catecholamine uptake, storage release and metabolism. Follicle survival, growth, hormone production and other functional parameters is being determined. These studies will delineate whether catecholamines are novel regulators of primate follicular growth and function. Emerging insights into the modes of actions of catecholamines in the primate ovary could provide the basis for treatments to normalize follicular growth and function in patients with PCOS, thereby restoring fertility.