Reversible infertility in a liver receptor homologue-1 (LRH-1)-knockdown mouse model
Han Gerrits A C , Marc C. B. C. Paradé A , Annemie M. C. B. Koonen-Reemst A , Nicole E. C. Bakker A , Lenita Timmer-Hellings A , Maarten D. Sollewijn Gelpke B and Jan A. Gossen A
+ Author Affiliations
- Author Affiliations
A Merck Sharp and Dohme Research Laboratories, Women’s Health Department, Molenstraat 110, 5342 CC, Oss, The Netherlands.
B Merck Sharp and Dohme Research Laboratories, Molecular Design and Informatics, Molenstraat 110, 5342 CC, Oss, The Netherlands.
C Corresponding author. Email: han.gerrits@merck.com
Reproduction, Fertility and Development 26(2) 293-306 https://doi.org/10.1071/RD12131
Submitted: 23 April 2012 Accepted: 22 December 2012 Published: 21 February 2013
Abstract
Liver receptor homologue-1 (LRH-1) is an orphan nuclear receptor that has been implicated in steroid hormone biosynthesis and fertility. Herein we describe a transgenic inducible short hairpin (sh) RNA mouse model that was used to study the effect of transient LRH-1 knockdown in vivo. Induction of expression of the shRNA directed against LRH-1 for 2–6 weeks resulted in 80% knockdown of LRH-1 protein in the ovary and complete infertility. Gonadotropin hyperstimulation could not rescue the observed defects in ovulation and corpus luteum formation in LRH-1-knockdown mice. The infertility phenotype was fully reversible because LRH-1-knockdown females became pregnant and delivered normal size litters and healthy pups after cessation of LRH-1 shRNA expression. Timed ovarian microarray analysis showed that, in line with the observed decrease in plasma progesterone levels, key steroid biosynthesis genes, namely Star, Cyp11a1, Hsd3b and Scarb1, were downregulated in LRH-1-knockdown ovaries. In contrast with what has been described previously, no clear effect was observed on oestrogenic activity in LRH-1-knockdown mice. Only Sult1e1 and, surprisingly, Hsd17b7 expression was modulated with potentially opposite effects on oestradiol bioavailability. In conclusion, the fully reversible infertility phenotype of LRH-1-knockdown mice shows the feasibility of an LRH-1 antagonist as new contraceptive therapy with a mechanism of action that most prominently affects cholesterol availability and progesterone production.
Additional keywords: estrogen, follicle culture, folliculogenesis and corpus luteum formation, microarray, NR5A2, ovary, progesterone, steroidogenesis.
References
Anderson, S. T., Isa, N. N., Barclay, J. L., Waters, M. J., and Curlewis, J. D. (2009). Maximal expression of suppressors of cytokine signaling in the rat ovary occurs in late pregnancy. Reproduction 138, 537–544.| Maximal expression of suppressors of cytokine signaling in the rat ovary occurs in late pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFOgtrjM&md5=418f5425119e8d3d515771f785c6a6f0CAS | 19502454PubMed |
Ashkenazi, H., Cao, X., Motola, S., Popliker, M., Conti, M., and Tsafriri, A. (2005). Epidermal growth factor family members: endogenous mediators of the ovulatory response. Endocrinology 146, 77–84.
| Epidermal growth factor family members: endogenous mediators of the ovulatory response.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtFGmt7jP&md5=9ec0eb753300edfe536e4473dd4f0a75CAS | 15459120PubMed |
Børglum, A. D., Hampson, M., Kjeldsen, T. E., Muir, W., Murray, V., Ewald, H., Mors, O., Blackwood, D., and Kruse, T. A. (2001). Dopa decarboxylase genotypes may influence age at onset of schizophrenia. Mol. Psychiatry 6, 712–717.
| Dopa decarboxylase genotypes may influence age at onset of schizophrenia.Crossref | GoogleScholarGoogle Scholar | 11673800PubMed |
Botrugno, O. A., Fayard, E., Annicotte, J. S., Haby, C., Brennan, O., Wendling, T., Tanaka, T., Kodama, T., Thomas, W., Aurwerx, J., and Schoonjans, K. (2004). Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Mol. Cell 15, 499–509.
| Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXns1ynurs%3D&md5=8fbd4b1c65bf79006e640c7d5022be1bCAS | 15327767PubMed |
Britt, K. L., Drummond, A. E., Dyson, M., Wreford, N. G., Jones, M. E., Simpson, E. R., and Findlay, J. K. (2001). The ovarian phenotype of the aromatase knockout (ArKO) mouse. J. Steroid Biochem. Mol. Biol. 79, 181–185.
| The ovarian phenotype of the aromatase knockout (ArKO) mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFyltbs%3D&md5=d5d9e312dda3083a18c1c04b143d3de1CAS | 11850223PubMed |
Burendahl, S., Treuter, E., and Nilsson, L. (2008). Molecular dynamics simulations of human LRH-1: the impact of ligand binding in a constitutively active nuclear receptor. Biochemistry 47, 5205–5215.
| Molecular dynamics simulations of human LRH-1: the impact of ligand binding in a constitutively active nuclear receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXks1Wntrc%3D&md5=3785d630467484465280e5b122a8acdaCAS | 18410128PubMed |
Chen, C. C., Hardy, D. B., and Mendelson, C. R. (2011). Progesterone receptor inhibits proliferation of human breast cancer cells via induction of MAPK phosphatase 1 (MKP-1/DUSP1). J. Biol. Chem. 286, 43 091–43 102.
| Progesterone receptor inhibits proliferation of human breast cancer cells via induction of MAPK phosphatase 1 (MKP-1/DUSP1).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1ShurjP&md5=2eac3ad183231054676646ebbe6ff559CAS |
Chu, C. P., Xu, C. J., Kannan, H., and Qiu,, D. L. (2012). Corticotrophin-releasing factor inhibits neuromedin U mRNA expressing neuron in the rat hypothalamic paraventricular nucleus in vitro. Neurosci. Lett. 511, 79–83.
| Corticotrophin-releasing factor inhibits neuromedin U mRNA expressing neuron in the rat hypothalamic paraventricular nucleus in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjtVOnu7g%3D&md5=9c79db095ddc8c84b0671f0df6a4ef68CAS | 22306094PubMed |
Clyne, C. D., Speed, C. J., Zhou, J., and Simpson, E. R. (2002). Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J. Biol. Chem. 277, 20 591–20 597.
| Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkslWgur4%3D&md5=dc27ecc702dc158fb77f832b433d5c7aCAS |
Conneely, O. M., Mulac-Jericevic, B., and Lydon, J. P. (2003). Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids 68, 771–778.
| Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXps1Oltb8%3D&md5=33e662c18a09b45e4cb06b116c55d920CAS | 14667967PubMed |
Coste, A., Dubuquoy, L., Barnouin, R., Annicotte, J. S., Magnier, B., Notti, M., Corazza, N., Antal, M. C., Metzger, D., Desreumaux, P., Brunner, T., Auwerx, J., and Schoonjans, K. (2007). LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Proc. Natl Acad. Sci. USA. 104, 13 098–13 103.
| LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpt1GgsL4%3D&md5=c0aa17a9b9e0c5579cebf16fe9dfc5aaCAS |
Huang da, W., Sherman, B. T., and Lempicki, R. A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57.
| Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.Crossref | GoogleScholarGoogle Scholar | 19131956PubMed |
de Veer, M. J., Sledz, C. A., and Williams, B. R. (2005). Detection of foreign RNA: implications for RNAi. Immunol. Cell Biol. 83, 224–228.
| Detection of foreign RNA: implications for RNAi.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmtVSitrY%3D&md5=20cc845433971f0bdd7fa0c39a4007ceCAS | 15877599PubMed |
Delerive, P., Galardi, C. M., Bisi, J. E., Nicodeme, E., and Goodwin, B. (2004). Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription. Mol. Endocrinol. 18, 2378–2387.
| Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXotFamsLg%3D&md5=3fbd1a19ff2268300174980e8e3413dfCAS | 15218078PubMed |
Duggavathi, R., Volle, D. H., Mataki, C., Antal, M. C., Messaddeq, N., Auwerx, J., Murphy, B. D., and Schoonjans, K. (2008). Liver receptor homolog 1 is essential for ovulation. Genes Dev. 22, 1871–1876.
| Liver receptor homolog 1 is essential for ovulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXovFWlsLo%3D&md5=2cc605570f2b6e211751d8d0a245f77bCAS | 18628394PubMed |
Elam, C., Hesson, L., Vos, M. D., Eckfeld, K., Ellis, C. A., Bell, A., Krex, D., Birrer, M. J., Latif, F., and Clark, G. J. (2005). RRP22 is a farnesylated, nucleolar, Ras-related protein with tumor suppressor potential. Cancer Res. 65, 3117–3125.
| 1:CAS:528:DC%2BD2MXjt1yktr0%3D&md5=98a5f195a6d9ac90d9c477f67cfd327bCAS | 15833841PubMed |
Ellinger-Ziegelbauer, H., Hihi, A. K., Laudet, V., Keller, H., Wahli, W., and Dreyer, C. (1994). FTZ-F1-related orphan receptors in Xenopus laevis: transcriptional regulators differentially expressed during early embryogenesis. Mol. Cell. Biol. 14, 2786–2797.
| FTZ-F1-related orphan receptors in Xenopus laevis: transcriptional regulators differentially expressed during early embryogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXksFWhtrg%3D&md5=7d91164e62199f15b948eaded50434cdCAS | 8139576PubMed |
Fayard, E., Auwerx, J., and Schoonjans, K. (2004). LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol. 14, 250–260.
| LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjvVemu74%3D&md5=8c5aecfa05bb70255571df6d47de5d5dCAS | 15130581PubMed |
Galarneau, L., Drouin, R., and Belanger, L. (1998). Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization. Cytogenet. Cell Genet. 82, 269–270.
| Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXksl2isQ%3D%3D&md5=d426dd3c1bf5c54398bf0d4821717e5fCAS | 9858833PubMed |
Gershon, E., Hourvitz, A., Reikhav, S., Maman, E., and Dekel, N. (2007). Low expression of COX-2, reduced cumulus expansion, and impaired ovulation in SULT1E1-deficient mice. FASEB J. 21, 1893–1901.
| Low expression of COX-2, reduced cumulus expansion, and impaired ovulation in SULT1E1-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmsVWks7o%3D&md5=6def116c8eede438886c2e30ddd79a7aCAS | 17341680PubMed |
Grigera, P. R., Ma, L., Borgman, C. A., Pinto, A. F., Sherman, N. E., Parsons, J. T., and Fox, J. W. (2012). Mass spectrometric analysis identifies a cortactin-RCC2/TD60 interaction in mitotic cells. J. Proteomics 75, 2153–2159.
| Mass spectrometric analysis identifies a cortactin-RCC2/TD60 interaction in mitotic cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xit12ht70%3D&md5=4dc14077d4887cfe8bbe4bb50645499fCAS | 22282019PubMed |
Gu, P., Goodwin, B., Chung, A. C.-K., Xu, X., Wheeler, D., Price, R. R., Galardi, C., Peng, L., Latour, A., Koller, B. H., Gossen, J., Kliever, S. A., and Cooney, A. J. (2005). Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Mol. Cell. Biol. 25, 3492–3505.
| Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjvFSmsbc%3D&md5=67973731639cc23975b355096ef1dfafCAS | 15831456PubMed |
Hakuno, N., Koji, T., Yano, T., Kobayashi, N., Tsutsumi, O., Taketani, Y., and Nakane, P. K. (1996). Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia. Endocrinology 137, 1938–1948.
| Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XisFCqsL4%3D&md5=5b8b9c003eff9fe0e1a34752df01ef68CAS | 8612534PubMed |
Hanson, G. R., Hoonakker, A. J., Alburges, M. E., McFadden, L. M., Robson, C. M., and Frankel, P. S. (2012). Response of limbic neurotensin systems to methamphetamine self-administration. Neuroscience 203, 99–107.
| Response of limbic neurotensin systems to methamphetamine self-administration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVOks7w%3D&md5=0f27848a9b5452604310c9e94306b1d8CAS | 22245499PubMed |
Hernandez-Gonzalez, I., Gonzalez-Robayna, I., Shimada, M., Wayne, C. M., Ochsner, S. A., White, L., and Richards, J. S. (2006). Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process? Mol. Endocrinol. 20, 1300–1321.
| Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XltlSrsLY%3D&md5=861410c17a3ec756c8138b4da9137f05CAS | 16455817PubMed |
Hibbert, M. L., Stouffer, R. L., Wolf, D. P., and Zelinski-Wooten, M. B. (1996). Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates. Proc. Natl Acad. Sci. USA 93, 1897–1901.
| Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhsFart78%3D&md5=e873f4c6524b5f669a908294682074e5CAS | 8700855PubMed |
Hinshelwood, M. M., Repa, J. J., Shelton, J. M., Richardson, J. A., Mangelsdorf, D. J., and Mendelson, C. R. (2003). Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function. Mol. Cell. Endocrinol. 207, 39–45.
| Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXntVyns7c%3D&md5=1d977ecefc1f8ce04988455cb8d0b5b8CAS | 12972182PubMed |
Hsia, N., Brousal, J. P., Hann, S. R., and Cornwall, G. A. (2005). Recapitulation of germ cell- and pituitary-specific expression with 1.6 kb of the cystatin-related epididymal spermatogenic (Cres) gene promoter in transgenic mice. J. Androl. 26, 249–257.
| 1:CAS:528:DC%2BD2MXis1Slu7w%3D&md5=81a87b6ce7993a5eb5fc9ec4d1f2e5deCAS | 15713831PubMed |
Jablonka-Shariff, A., and Olson, L. M. (1998). The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. Endocrinology 139, 2944–2954.
| The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjsFSksrg%3D&md5=817350158a534842942267057e141364CAS | 9607805PubMed |
Jacob, F., Ukegjini, K., Nixdorf, S., Ford, C. E., Olivier, J., Caduff, R., Scurry, J. P., Guertler, R., Hornung, D., Mueller, R., Fink, D. A., Hacker, N. F., and Heinzelmann-Schwarz, V. A. (2012). Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients. PLoS One 7, e31885.
| Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjsVaqsbc%3D&md5=94c7d8746c381610964f7288e1feb678CAS | 22363760PubMed |
Jo, M., and Curry, T. E., (2006). Luteinizing hormone-induced RUNX1 regulates the expression of genes in granulosa cells of rat periovulatory follicles. Mol. Endocrinol. 20, 2156–2172.
| Luteinizing hormone-induced RUNX1 regulates the expression of genes in granulosa cells of rat periovulatory follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Cqu78%3D&md5=69cd86880dc63ebbf0850782d3095404CAS | 16675540PubMed |
Kimura, J., Kudoh, T., Miki, Y., and Yoshida, K. (2011). Identification of dihydropyrimidinase-related protein 4 as a novel target of the p53 tumor suppressor in the apoptotic response to DNA damage. Int. J. Cancer 128, 1524–1531.
| Identification of dihydropyrimidinase-related protein 4 as a novel target of the p53 tumor suppressor in the apoptotic response to DNA damage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1els7Y%3D&md5=c1bdc780c9ecc07b5afda33957322ebfCAS | 20499313PubMed |
Kudo, T., and Sutou, S. (1997). Molecular cloning of chicken FTZ-F1-related orphan receptors. Gene 197, 261–268.
| Molecular cloning of chicken FTZ-F1-related orphan receptors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlsFGmsL8%3D&md5=dd15c6ee997adeae0930e13e56259aa9CAS | 9332374PubMed |
Kumar, T. R., Wang, Y., Lu, N., and Matzuk, M. M. (1997). Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat. Genet. 15, 201–204.
| Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhtVOks7c%3D&md5=2825d99f3f9b1aa021c4a74c96931c4bCAS | 9020850PubMed |
Labelle-Dumais, C., Paré, J. F., Bélanger, L., Farookhi, R., and Dufort, D. (2007). Impaired progesterone production in Nr5a2+/– mice leads to a reduction in female reproductive function. Biol. Reprod. 77, 217–225.
| Impaired progesterone production in Nr5a2+/– mice leads to a reduction in female reproductive function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXot1OnsLg%3D&md5=fb2f38a5b58e4bb612a1ef0b1e447f53CAS | 17409375PubMed |
Le, J. A., Wilson, H. M., Shehu, A., Mao, J., Devi, Y. S., Halperin, J., Aguilar, T., Seibold, A., Maizels, E., and Gibori, G. (2012). Generation of mice expressing only the long form of the prolactin receptor reveals that both isoforms of the receptor are required for normal ovarian function. Biol. Reprod. 86, 86.
| Generation of mice expressing only the long form of the prolactin receptor reveals that both isoforms of the receptor are required for normal ovarian function.Crossref | GoogleScholarGoogle Scholar | 22190699PubMed |
Lee, Y. K., Schmidt, D. R., Cummins, C. L., Choi, M., Peng, L., Zhang, Y., Goodwin, B., Hammer, R. E., Mangelsdorf, D. J., and Kliewer, S. A. (2008). Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis. Mol. Endocrinol. 22, 1345–1356.
| Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXntFajtrg%3D&md5=e0868577b89f34547f1d4e275693cc7cCAS | 18323469PubMed |
Lin, W.-W., Wang, H.-W., Sum, C., Liu, D., Hew, C. L., and Chung, B.-C. (2000). Zebrafish ftz-f1 gene has two promoters, is alternatively spliced, and is expressed in digestive organs. Biochem. J. 348, 439–446.
| Zebrafish ftz-f1 gene has two promoters, is alternatively spliced, and is expressed in digestive organs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXksF2mtrc%3D&md5=f85dc768b7f8c3ef945d5c9de424e893CAS |
Luo, Y., Liang, C. P., and Tall, A. R. (2001). The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J. Biol. Chem. 276, 24 767–24 773.
| The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlt1agtrg%3D&md5=d711fe91e3a419ade4ab8a1b6d49d5a0CAS |
Maman, E., Yung, Y., Cohen, B., Konopnicki, S., Dal Canto, M., Fadini, R., Kanety, H., Kedem, A., Dor, J., and Hourvitz, A. (2011). Expression and regulation of sFRP family members in human granulosa cells. Mol. Hum. Reprod. 17, 399–404.
| Expression and regulation of sFRP family members in human granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnvVKms7k%3D&md5=d8a60495e9dd796926156a3bd2dd6ce6CAS | 21307090PubMed |
Mataki, C., Magnier, B. C., Houten, S. M., Annicotte, J. S., Argmann, C., Thomas, C., Overmars, H., Kulik, W., Metzger, D., Auwerx, J., and Schoonjans, K. (2007). Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1. Mol. Cell. Biol. 27, 8330–8339.
| Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVeisL7L&md5=e74b8ff813a16a9e64a81cd1bf95d624CAS | 17908794PubMed |
Mueller, M., Cima, I., Noti, M., Fuhrer, A., Jakob, S., Dubuquoy, L., Schoonjans, K., and Brunner, T. (2006). The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine. J. Exp. Med. 203, 2057–2062.
| The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XptlSgs74%3D&md5=6c7660ccc503595dceef47f34f1fd682CAS | 16923850PubMed |
Nyegaard, M., Overgaard, M. T., Su, Y. Q., Hamilton, A. E., Kwintkiewicz, J., Hsieh, M., Nayak, N. R., Conti, M., Conover, C. A., and Giudice, L. C. (2010). Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility. Biol. Reprod. 82, 1129–1138.
| Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmvVCgt7g%3D&md5=46a810378cfd3e9e6c1c66e763b55a2eCAS | 20130263PubMed |
Oh, Y. S., Shin, S., Lee, Y. J., Kim, E. H., and Jun, H. S. (2011). Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors. PLoS One 6, e23894.
| Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SqtL7L&md5=004a33d619ffb781f1b72365b47f0275CAS | 21897861PubMed |
Ortlund, E. A., Lee, Y., Solomon, I. H., Hager, J. M., Safi, R., Choi, Y., Guan, Z., Tripathy, A., Raetz, C. R., McDonnell, D. P., Moore, D. D., and Redinbo, M. R. (2005). Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nat. Struct. Mol. Biol. 12, 357–363.
| Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXivFWjtLg%3D&md5=fb421e05812b9660970ba6e7b32a150dCAS | 15723037PubMed |
Out, C., Hageman, J., Bloks, V. W., Gerrits, H., Sollewijn Gelpke, M. D., Bos, T., Havinga, R., Smit, M. J., Kuipers, F., and Groen, A. K. (2011). Liver receptor homolog-1 is critical for adequate up-regulation of Cyp7a1 gene transcription and bile salt synthesis during bile salt sequestration. Hepatology 53, 2075–2085.
| Liver receptor homolog-1 is critical for adequate up-regulation of Cyp7a1 gene transcription and bile salt synthesis during bile salt sequestration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmsFCqtLs%3D&md5=aa21c62357f6b87f9ac7e7f8b836333dCAS | 21391220PubMed |
Pare, J. F., Malenfant, D., Courtemanche, C., Jacob-Wagner, M., Roy, S., Allard, D., and Belanger, L. (2004). The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J. Biol. Chem. 279, 21 206–21 216.
| The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjvV2ntLg%3D&md5=60a0ee9981d1c70c358d1b82294d8125CAS |
Richards, J. S., and Pangas, S. A. (2010). The ovary: basic biology and clinical implications. J. Clin. Invest. 120, 963–972.
| The ovary: basic biology and clinical implications.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksVChsrk%3D&md5=86ac5ed499d36554efa9be7e9aafc438CAS | 20364094PubMed |
Robker, R. L., and Richards, J. S. (1998). Hormone-induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1. Mol. Endocrinol. 12, 924–940.
| Hormone-induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXktlOisLo%3D&md5=4a9c0a8beabe37f0f5f85e1212c92bcbCAS | 9658398PubMed |
Robker, R. L., Russell, D. L., Espey, L. L., Lydon, J. P., O’Malley, B. W., and Richards, J. S. (2000). Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc. Natl Acad. Sci. USA 97, 4689–4694.
| Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXivFKjtLw%3D&md5=452860e47b66e6a835c2c625a5b9bb8dCAS | 10781075PubMed |
Rose, U. M., Hanssen, R. G., and Kloosterboer, H. J. (1999). Development and characterization of an in vitro ovulation model using mouse ovarian follicles. Biol. Reprod. 61, 503–511.
| Development and characterization of an in vitro ovulation model using mouse ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXkslKqt7g%3D&md5=4760dad7ddb55cd09fa2c9728e9f6d9dCAS | 10411533PubMed |
Schoonjans, K., Annicotte, J.-S., Huby, T., Botrugno, O. A., Fayard, E., Ueda, Y., Chapman, J., and Auwerx, J. (2002). Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I. EMBO Rep. 3, 1181–1187.
| Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtVGmtLs%3D&md5=0c6d1fe44ff4802615d57528d16420acCAS | 12446566PubMed |
Schoonjans, K., Dubuquoy, L., Mebis, J., Fayard, E., Wendling, O., Haby, C., Geboes, K., and Auwerx, J. (2005). Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation. Proc. Natl Acad. Sci. USA 102, 2058–2062.
| Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhvFGru7Y%3D&md5=560c4a036c7b08d859b6247c4532aa6eCAS | 15684064PubMed |
Seibler, J., Kleinridders, A., Küter-Luks, B., Niehaves, S., Brüning, J. C., and Schwenk, F. (2007). Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic Acids Res. 35, e54.
| Reversible gene knockdown in mice using a tight, inducible shRNA expression system.Crossref | GoogleScholarGoogle Scholar | 17376804PubMed |
Shehu, A., Mao, J., Gibori, G. B., Halperin, J., Le, J., Devi, Y. S., Merrill, B., Kiyokawa, H., and Gibori, G. (2008). Prolactin receptor-associated protein/17beta-hydroxysteroid dehydrogenase type 7 gene (Hsd17b7) plays a crucial role in embryonic development and fetal survival. Mol. Endocrinol. 22, 2268–2277.
| Prolactin receptor-associated protein/17beta-hydroxysteroid dehydrogenase type 7 gene (Hsd17b7) plays a crucial role in embryonic development and fetal survival.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Sgt7bL&md5=f4c85beca03446dda1575518f724e406CAS | 18669642PubMed |
Shirasuna, K., Shimizu, T., Hayashi, K. G., Nagai, K., Matsui, M., and Miyamoto, A. (2007). Positive association, in local release, of luteal oxytocin with endothelin 1 and prostaglandin F2alpha during spontaneous luteolysis in the cow: a possible intermediatory role for luteolytic cascade within the corpus luteum. Biol. Reprod. 76, 965–970.
| Positive association, in local release, of luteal oxytocin with endothelin 1 and prostaglandin F2alpha during spontaneous luteolysis in the cow: a possible intermediatory role for luteolytic cascade within the corpus luteum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlvFGmsrY%3D&md5=64bd0363552b95ca87ee9d69f11dbe6bCAS | 17287495PubMed |
Sicinski, P., Donaher, J. L., Geng, Y., Parker, S. B., Gardner, H., Park, M. Y., Robker, R. L., Richards, J. S., McGinnis, L. K., Biggers, J. D., Eppig, J. J., Bronson, R. T., Elledge, S. J., and Weinberg, R. A. (1996). Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 384, 470–474.
| Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XnsFWqurc%3D&md5=d8306e276cefd9adfec1fb86d529e872CAS | 8945475PubMed |
Sirianni, R., Seely, J. B., Attia, G., Stocco, D. M., Carr, B. R., Pezzi, V., and And Rainey, W. E. (2002). Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes. J. Endocrinol. 174, R13–R17.
| Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnslGju74%3D&md5=c1a5e156b230e87347886d7af7682cf4CAS | 12208674PubMed |
Sriraman, V., Sinha, M., and Richards, J. S. (2010). Progesterone receptor-induced gene expression in primary mouse granulosa cell cultures. Biol. Reprod. 82, 402–412.
| Progesterone receptor-induced gene expression in primary mouse granulosa cell cultures.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVSnsbs%3D&md5=c96e90597c2671d1c9e3b5f8a118c704CAS | 19726735PubMed |
Sun, L., Peng, Y., Sharrow, A. C., Iqbal, J., Zhang, Z., Papachristou, D. J., Zaidi, S., Zhu, L. L., Yaroslavskiy, B. B., Zhou, H., Zallone, A., Sairam, M. R., Kumar, T. R., Bo, W., Braun, J., Cardoso-Landa, L., Schaffler, M. B., Moonga, B. S., Blair, H. C., and Zaidi, M. (2006). FSH directly regulates bone mass. Cell. 125, 247–260.
| FSH directly regulates bone mass.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xkt1Oqtbs%3D&md5=9eebca89cc8ab0762c0ccdd1f71cd1d9CAS | 16630814PubMed |
van Casteren, J. I., Schoonen, W. G., and Kloosterboer, H. J. (2000). Development of time-resolved immunofluorometric assays for rat follicle-stimulating hormone and luteinizing hormone and application on sera of cycling rats. Biol. Reprod. 62, 886–894.
| Development of time-resolved immunofluorometric assays for rat follicle-stimulating hormone and luteinizing hormone and application on sera of cycling rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXitFajt7o%3D&md5=e240bb8f2a6c4fc6298e76d8f6c78ba6CAS | 10727257PubMed |
Venteclef, N., Smith, J. C., Goodwin, B., and Delerive, P. (2006). Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response. Mol. Cell. Biol. 26, 6799–6807.
| Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Clur0%3D&md5=67cc8eb3e49ab4c5f31fd5f5ca4597a6CAS | 16943422PubMed |
Venteclef, N., Jakobsson, T., Steffensen, K. R., and Treuter, E. (2011). Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol. Metab. 22, 333–343.
| Metabolic nuclear receptor signaling and the inflammatory acute phase response.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXps1ymur0%3D&md5=99c2521d0146d7c56552896630686f9bCAS | 21646028PubMed |
Whitby, R. J., Dixon, S., Maloney, P. R, Delerive, P., Goodwin, B. J, Parks, D. J, and Willson, T. M. (2006). Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1. J. Med. Chem. 49, 6652–6655.
| Identification of small molecule agonists of the orphan nuclear receptors liver receptor homolog-1 and steroidogenic factor-1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtV2gtLnI&md5=21f05c844aade33d90440a7691f0c2b0CAS | 17154495PubMed |
Whitby, R. J., Stec, J., Blind, R. D., Dixon, S., Leesnitzer, L. M., Orband-Miller, L. A., Williams, S. P., Willson, T. M., Xu, R., Zuercher, W. J., Cai, F., and Ingraham, H. A. (2011). Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). J. Med. Chem. 54, 2266–2281.
| Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXivFyisrg%3D&md5=63d3a525b6524a6a0c4ae556bd2684e0CAS | 21391689PubMed |
