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. This ongoing project is examining the hypothesis that growth factor molecules known as neurotrophins, and chemical messengers required for the development and mature function of the nervous system are produced by the mammalian ovary and contribute to regulating critical developmental phases in the natural history of the gland. The analysis of mutant mice carrying deletions of the genes encoding either neurotrophins or their recognition molecules (i.e., the neurotrophin receptors) showed that these growth factors are required for early development of ovarian follicles (the structural and functional unit of the ovary). In addition to neurotrophins, the ovary produces a variety of the same chemical messengers required for neuron-to-neuron communication in the nervous system. These messengers, known as neurotransmitters, appear to contribute to the process by which follicles become differentiated during early development and acquire the capability of responding to those hormones that -- secreted by the pituitary gland -- control the growth of mature follicles before puberty and during adult reproductive life. We are currently carrying out studies aimed at defining the cell types able to recognize neurotrophins during ovarian development, and are using genetic means to define the importance of these recognition molecules in ovarian development, including ovulation. We are also investigating the hypothesis that an excess of neurotrophins is deleterious, instead of beneficial, to ovarian function.
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