Genomes and Genes
NEURAL CONTROL OF THE PREPUBERTAL OVARY
Principal Investigator: Sergio Ojeda
Affiliation: Oregon Health and Science University
Abstract: DESCRIPTION: (Adapted from the applicant's abstract) This is a renewal application aimed at elucidating some of the basic neuroendocrine and cellular mechanisms overning mammalian ovarian development. During the last period of support we employed a combination of cellular, molecular and genetic approaches to demonstrate the existence of a neurotrophin-mediated regulatory system that is acting at the interface between the endocrine and nervous systems -- contributes to the developmental control of ovarian function. In related studies, we identified a series of additional genes that may belong to the hierarchy of regulatory molecules controlling ovarian folliculogenesis, follicular growth and ovulation. The recognition of these new regulatory components, and the use of genetic approaches to modify the expression of genes in a cell-specific and temporally restricted manner, provides us with a new opportunity to unravel some of the key cell-cell regulatory mechanisms underlying mammalian ovarian development. To initiate this undertaking we propose two sets of studies: The first, to define the physiological importance of NGF and its receptors I follicular growth and ovulation, and their contribution to the etiology of ovarian cystic disease; the other, to elucidate the role that a set of functionally diverse genes found to be differentially expressed in the ovary at two key developmental phases (folliculogenesis and first ovulation) may play in the regulation of these processes. To this end, the following specific aims are proposed: 1. To test the hypothesis that, while required for normal follicular growth, NGF overproduction in endocrine cells of the follicular wall leads to the development of cystic ovarian disease via activation of the low-affinity neurotrophin receptor, p75NGFR. 2. To examine the hypothesis that activation of trkA, the high ffinity tyrosine kinase NGF receptor, in ovarian endocrine cells of mesenchymal origin contributes to the completion of two critical phases in the natural history of the developing ovary, the initiation of preantral follicular development and rupture of the follicular wall at ovulation. 3. To define the role that insulin receptor-related receptor (IRR), an orphan receptor of the insulin receptor family recently found to be co-expressed with trkA in thecal cells of periovulatory follicles, plays in ovulation, and to molecularly identify the gene encoding the IRR ligand. 4. To test the hypothesis that follicular formation requires the temporal and cell-specific coordinated expression of three functionally diverse genes found to be differentially displayed at the time of folliculogenesis; the adhesion molecule Cadherin-11, the protooncogene PTTG, and the transcriptional regulator ENX-1.
Funding Period: 1988-02-01 - 2007-03-31
more information: NIH RePORT
- Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovaryLars Kunz
Anatomical Institute, University of Munich, Biedersteiner Str 29, Munich, Germany
J Cell Physiol 206:167-74. 2006..Our data might also be important for Kv4 channels in the brain and the cardiovascular system where rapid steroid effects are discussed in the context of prevention of cell death...
- NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovaryBredford Kerr
Division of Neuroscience, Oregon National Primate Research Center Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA
Reproduction 138:131-40. 2009..They also suggest that a mechanism by which NTRK2 receptors facilitate subsequent follicle development is by inducing the formation of functional FSHR...
- Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humansGregory A Dissen
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006 3448, USA
Endocrinology 150:2906-14. 2009....
- Role of neurotrophic factors in early ovarian developmentGregory A Dissen
Division of Neuroscience, Oregon National Primate Research Center Oregon Health and Science University, Beaverton, Oregon 97006 3448, USA
Semin Reprod Med 27:24-31. 2009..Altogether, these observations indicate that NTs are important contributors to the gonadotropin-independent process underlying the formation and initiation of ovarian follicular growth...
- Fbxw15/Fbxo12J is an F-box protein-encoding gene selectively expressed in oocytes of the mouse ovaryElsa de la Chesnaye
UIM en Biología del Desarrollo, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Biol Reprod 78:714-25. 2008..The specific expression of Fbxw15/Fbxp12J in oocytes and its developmental pattern of expression suggest a role for this gene in the regulation of oocyte physiology...
- Functional development of the ovarian noradrenergic innervationManuel Ricu
Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, P O Box 233, Santiago 1 838 0492, Chile
Endocrinology 149:50-6. 2008..These results indicate that vesicular release of NE from ovarian noradrenergic nerves begins to operate by the third week of postnatal life, becoming fully functional near the time of puberty...
- Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesisCecilia Garcia-Rudaz
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
Development 134:945-57. 2007..As an endoplasmic reticulum-bound peptidase, Fxna may facilitate follicular organization by processing precursor proteins required for intraovarian cell-to-cell communication...
- FSH regulates acetycholine production by ovarian granulosa cellsArtur Mayerhofer
Anatomisches Institut der Universität München, Deutschland
Reprod Biol Endocrinol 4:37. 2006..To gain further insights into the possible role of ACh in the ovary, we examined ChAT expression in the gland before and after birth, as well as in adults, and studied the regulation of ACh production by FSH...
- Origin and ontogeny of mammalian ovarian neuronsW Les Dees
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A and M University, College Station, Texas 77845 4458, USA
Endocrinology 147:3789-96. 2006..Results demonstrate that p75NTR-expressing ovarian neurons originate from the neural crest and that a catecholaminergic subset is associated with pubertal maturation of the ovary and subsequent reproductive function...
- Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretionC Salas
, , Facultad de Medicina, Hospital Clinico J. J. Aguirre, Universidad de Chile, Santos Dumont 999 Independencia, Santiago 838-0456, Chile
J Clin Endocrinol Metab 91:2396-403. 2006..NGF stimulates E(2) secretion both directly and by increasing the formation of FSHRs...
- Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovaryGregory A Dissen
Division of Neuroscience, Oregon Regional Primate Research Center, 505 N W 185th Avenue, Beaverton, Oregon 97006 3448, USA
Endocrinology 147:155-65. 2006....
- Loss of synaptonemal complex protein-1, a synaptonemal complex protein, contributes to the initiation of follicular assembly in the developing rat ovaryAlfonso Paredes
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, 97006, USA
Endocrinology 146:5267-77. 2005..SCP1-deficient ovaries exhibited an increased number of newly formed follicles, suggesting that completion of meiotic prophase I endows oocytes with the ability to orchestrate follicular assembly...
- In vivo manipulation of gene expression in non-human primates using lentiviral vectors as delivery vehiclesGregory A Dissen
Division of Neuroscience, Oregon National Primate Research Center Oregon Health and Science University, Beaverton, OR 97006 3448, USA
Methods 49:70-7. 2009..Finally, we describe in detail the lentiviral vector production protocol we use and provide examples of how the vector can be employed to target peripheral tissues and the brain...