BES2002 Symposia Hormonal Control of Female Reproduction (4 abstracts)
Role of cofactors for nuclear receptors in reproduction
SR Milligan 1 , R White 2 , G Leonardsson 2 , M Soulez 2 , M Jacobs 3 , I Rosewell 3 & M Parker 2
1School of Biomedical Sciences, Kings College London, London, U.K; 2Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, London, UK; 3Transgenic Unit, ICRF Clare Hall Laboratories, South Mimms, UK.
Nuclear receptors regulate biological responses by acting as ligand dependent transcription factors in target cells. Their ability to modulate transcription is mediated by cofactors which are recruited to target genes by binding to receptors. They can either act as coactivators or corepressors and their roles include their ability to remodel chromatin and to recruit the basic transcription machinery. NRIP1 is transcriptional repressor which is recruited to nuclear receptors in a ligand-dependent manner and so it may have a role in switching off genes in specific cell types at specific times. To investigate the role of NRIP1 we have generated mice devoid of the gene. NRIP1 null mice are viable, born in the expected mendelian ratio when heterozygotes are crossed but are retarded in their growth compared with their normal littermates. Females are completely infertile caused by an ovulation defect in which mature follicles fail to release oocytes. Despite the failure of mature follicles to ovulate they do undergo luteinisation, superficially resembling the 'luteinised unruptured follicle' syndrome seen in women. Superovulation and ovarian transfer experiments indicate that the primary defect is in the ovary itself and not in the hypothalamic-pituitary axis. The phenotype of NRIP1 mice resembles that of progesterone receptor and Cox 2 null mice but alterations in the expression of these two genes does not seem to account for the failure of NRIP1 null mice to ovulate. On the other hand kallikrein gene expression is markedly up-regulated in the ovaries of NRIP1 null mice and we are investigating the potential role of this family of proteases in ovulation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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