Our long-term goal is to further our understanding of the molecular mechanisms by which FSH initiates ovarian follicular development. Following the elevation of intracellular cAMP levels by FSH, the adenylyl cyclase enzyme exhibits a transient attenuation response.
In specific aim one, we will investigate possible mechanisms responsible for the transient attenuation of the granulosa cell adenylate cyclase enzyme. cAMP Induces all of the differentiation-associated effects in immature granulosa cells attributed to FSH; thus cAMP Is believed to mediate these actions of FSH. Yet, identification and characterization of the enzymes which mediate the effects of cAMP, the cAMP dependent protein kinases, is not available. In the next three specific aims, we will identify the subunit composition of the cAMP-dependent protein kinases present in immature porcine granulosa cells, we will elucidate the acute regulation of this enzyme by cAMP in response to FSH, and we will identify proteins which are phosphorylated in this cascade. Although relatively low levels of cAMP are needed to promote granulosa cell maturation, pharmacologically high levels of cAMP are not deleterious.
In specific aim five we will investigate mechanisms which protect the granulosa cells from excessively high intracellular cAMP levels. It is hoped that these studies will extend our understanding of the molecular mechanisms by which FSH via cAMP regulates granulosa cell function.
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