PTGER1 and PTGER2 receptors mediate regulation of progesterone synthesis and type 1 11β-hydroxysteroid dehydrogenase activity by prostaglandin E2 in human granulosa–lutein cells

In luteinizing granulosa cells, prostaglandin E2 (PGE2) can exert luteotrophic actions, apparently via the cAMP signalling pathway. In addition to stimulating progesterone synthesis, PGE2 can also stimulate oxidation of the physiological glucocorticoid, cortisol, to its inactive metabolite, cortisone, by the type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme in human granulosa–lutein cells. Having previously shown these human ovarian cells to express functional G-protein coupled, E-series prostaglandin (PTGER)1, PTGER2 and PTGER4 receptors, the aim of this study was to delineate the roles of PTGER1 and PTGER2 receptors in mediating the effects of PGE2 on steroidogenesis and cortisol metabolism in human granulosa–lutein cells. PGE2-stimulated concentration-dependent increases in both progesterone production and cAMP accumulation (by 1·9±0·1- and 18·7±6·8-fold respectively at 3000 nM PGE2). While a selective PTGER1 antagonist, SC19220, could partially inhibit the steroidogenic response to PGE2 (by 55·9±4·1% at 1000 nM PGE2), co-treatment with AH6809, a mixed PTGER1/PTGER2 receptor antagonist, completely abolished the stimulation of progesterone synthesis at all tested concentrations of PGE2 and suppressed the stimulation of cAMP accumulation. Both PGE2 and butaprost (a preferential PTGER2 receptor agonist) stimulated concentration-dependent increases in cortisol oxidation by 11βHSD1 (by 42·5±3·1 and 40·0±3·0% respectively, at PGE2 and butaprost concentrations of 1000 nM). Co-treatment with SC19220 enhanced the ability of both PGE2 and butaprost to stimulate 11βHSD1 activity (by 30·2±0·2 and 30·5±0·6% respectively), whereas co-treatment with AH6809 completely abolished the 11βHSD1 responses to PGE2 and butaprost. These findings implicate the PTGER2 receptor–cAMP signalling pathway in the stimulation of progesterone production and 11βHSD1 activity by PGE2 in human granulosa–lutein cells

MUGEN mouse database; Animal models of human immunological diseases

The MUGEN mouse database (MMdb) (www.mugen-noe.org/database/) is a database of murine models of immune processes and immunological diseases. Its aim is to share and publicize information on mouse strain characteristics and availability from participating institutions. MMdb's basic classification of models is based on three major research application categories: Models of Human Disease, Models of Immune Processes and Transgenic Tools. Data on mutant strains includes detailed information on affected gene(s), mutant allele(s) and genetic background (DNA origin, gene targeted, host and backcross strain background). Each gene/transgene index also includes IDs and direct links to Ensembl, ArrayExpress, EURExpress and NCBI's Entrez Gene database. Phenotypic description is standardized and hierarchically structured, based on MGI's mammalian phenotypic ontology terms. Availability (e.g. live mice, cryopreserved embryos, sperm and ES cells) is clearly indicated, along with handling and genotyping details (in the form of documents or hyperlinks) and all relevant contact information (including EMMA and Jax/IMSR hyperlinks where available). MMdb's design offers a user-friendly query interface and provides instant access to the list of mutant strains and genes. Database access is free of charge and there are no registration requirements for data querying

CreZOO-the European virtual repository of Cre and other targeted conditional driver strains

The CreZOO (http://www.crezoo.org/) is the European virtual repository of Cre and other targeted conditional driver strains. These mice serve as tools for researchers to selectively ‘switch off’ gene expression in mouse models to examine gene function and disease pathology. CreZOO aims to capture and disseminate extant and new information on these Cre driver strains, such as genetic background and availability information, and details pertaining promoter, allele, inducibility and expression patterns, which are also presented. All transgenic strains carry detailed information according to MGI's official nomenclature, whereas their availability [e.g. live mice, cryopreserved embryos, sperm and embryonic stem (ES) cells] is clearly indicated with links to European and International databases and repositories (EMMA, MGI/IMSR, MMRRC, etc) and laboratories where the particular mouse strain is available together with the respective IDs. Each promoter/gene includes IDs and direct links to MGI, Entrez Gene, Ensembl, OMIM and RGD databases depending on their species origin, whereas allele information is presented with MGI IDs and active hyperlinks to redirect the user to the respective page in a new tab. The tissue/cell (special) and developmental (temporal) specificity expression patterns are clearly presented, whereas handling and genotyping details (in the form of documents or hyperlinks) together with all relevant publications are clearly presented with PMID(s) and direct PubMed links. CreZOO's design offers a user-friendly query interface and provides instant access to the list of conditional driver strains, promoters and inducibility details. Database access is free of charge and there are no registration requirements for data querying. CreZOO is being developed in the context of the CREATE consortium (http://www.creline.org/), a core of major European and international mouse database holders and research groups involved in conditional mutagenesis