| progesterone receptor | OKDB#: 333 |
| Symbols: | PGR | Species: | human | ||
| Synonyms: | PR, NR3C3 | Locus: | 11q22.1 in Homo sapiens | HPMR |
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| General Comment |
The progesterone signal is known to be mediated initially by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most tissues studied, the PR is induced by ovarian estrogen via the estrogen receptor (ER), thereby implying that many of the observed reproductive physiological responses attributed to PR could conceivably be due to the combined effects of progesterone and estrogen.
NCBI Summary: This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015] |
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| General function | Receptor, Nucleic acid binding, DNA binding, Transcription factor | ||||
| Comment | Progesterone Inhibits Oxytocin- and Prostaglandin F2alpha-Stimulated Increases in Intracellular Calcium Concentrations in Small and Large Ovine Luteal Cells. Davis TL et al. There is increasing evidence that the corpus luteum plays an important role in regulating its own demise. A series of experiments was performed to study the effects of luteal concentrations of progesterone on the functions of steroidogenic luteal cells. In the first experiment steroidogenic small luteal cells (SLC) were separated from endothelial cells and it was determined that it was the SLC which contained receptors for oxytocin. Treatment with progesterone (95 microM) for as little as 1 h decreased (P < 0.05) the percent of SLC responding to oxytocin (10 microM) with an increase in intracellular concentrations of calcium and this effect continued for the duration of the experiment. In a second experiment the response to oxytocin was increased (P < 0.05) by 3 h following progesterone removal with a further increase by 16 h. The ability of 1 microM PGF(2alpha) to increase intracellular concentrations of calcium was also decreased (P < 0.05) by progesterone treatment. By three hours following removal of progesterone the percent of steroidogenic large luteal cells (LLC) responding to PGF(2alpha) was increased and not different from that observed in cells 16 h after progesterone removal. Finally cyclodextrins (MbetaCD) were used to remove cholesterol from the plasma membrane of luteal cells and MbetaCD loaded with cholesterol was used to put cholesterol back into the plasma membrane of progesterone-treated cells. Treatment with MbetaCD reduced (P < 0.05) the responsiveness of SLC to oxytocin and LLC to PGF(2alpha). Use of cholesterol loaded MbetaCD returned the responsiveness of both SLC and LCC treated with progesterone to that observed in vehicle (no progesterone) treated controls. In summary, intraluteal concentrations of progesterone inhibit the ability of oxytocin to increase intracellular concentrations of calcium in SLC and the ability of PGF(2alpha) to increase intracellular concentrations of calcium in LLC. The highest concentration of progesterone appears to act by influencing cholesterol content of the luteal cell membranes. | ||||
| Cellular localization | Nuclear | ||||
| Comment | Subcellular localization and transcriptional activity of green fluorescent protein-progesterone receptor A and B chimeras (GFP-PRA and GFP-PRB) were examined in living mammalian cells. The two forms of the receptor were found to have distinct intracellular distributions; GFP-PRA was found to be more nuclear than GFP-PRB in four cell lines examined (Lim et al., 1999). Peluso JJ, et al 2001 reported the characterization of a putative membrane receptor for progesterone in rat granulosa cells. | ||||
| Ovarian function | Initiation of primordial follicle growth, Follicle atresia, Ovulation, Steroid metabolism, Luteinization, Luteolysis, Oocyte growth, Oocyte maturation | ||||
| Comment | Progesterone Increases Mitochondria Membrane Potential in Non-human Primate Oocytes and Embryos. Dai Q et al. (2020) Mitochondrial activity is critical and correlates with embryo development. The identification of a novel human mitochondrial progesterone receptor (PR-M) that increases cellular respiration brings into question a role for progesterone in oocyte and preimplantation embryo development. Oocytes and embryos were generated from three Rhesus non-human primates (Macaca mulatta) undergoing in vitro fertilization. Immunohistochemical (IHC) staining for the progesterone receptor and mitochondria, RT-PCR with product sequencing for a mitochondrial progesterone receptor, and mitochondrial membrane determination with JC-1 staining were performed. IHC staining with selective antibodies to the progesterone receptor showed non-nuclear staining. Staining was absent in mouse control embryos. RT-PCR with product sequencing demonstrated PR-M transcript in Rhesus oocytes and embryos, which was absent in mouse embryos. Treatment of Rhesus oocytes and embryos with progesterone showed increased mitochondrial membrane potential, which was absent in mouse embryos. Our results support that progesterone increases mitochondrial membrane potential in oocytes and developing embryos. This is likely an in vivo mechanism to support preimplantation embryo development, and brings up the possibility of in vitro manipulation of culture media for optimization of growth.////////////////// Dienogest suppresses the activation of primordial follicles and preserves the primordial follicle stockpile for fertility in mice. Zheng L et al. (2018) The aim of the present study was to characterize the effect of long-term usage of dienogest, a fourth-generation progestin that possesses progestogen and anti-androgen activities, on the stockpile of oocytes and fertility after administration. Female ICR mice (100 days old) were divided into a dienogest group and a control group. The mice received 16 consecutive subcutaneous injections of 5 mg dienogest dissolved in corn oil or corn oil as a vehicle control every 4 days. The mice treated with dienogest had more total offspring and larger litter sizes after the final administration than the mice treated with the vehicle control. Greater numbers of primordial follicles were detected at both 4 and 80 days after the final administration. No significant differences were found in serum anti-Müllerian hormone concentrations at 4 and 80 days after the final dienogest administration. The ratio of primary to primordial follicles was decreased in 3-day-old newborn ovaries cultured for 4 days with dienogest (10-7, 10-6and 10-5mol/l) compared with ovaries cultured without dienogest. The results of the present study indicate that dienogest suppresses the activation of primordial follicles during its administration and preserves the primordial follicle stockpile and subsequent fertility in mice.////////////////// Arrest at the diplotene stage of meiotic prophase I is delayed by progesterone but is not required for primordial follicle formation in mice. Dutta S et al. (2016) In mammalian females, reproductive capacity is determined by the size of the primordial follicle pool. During embryogenesis, oogonia divide mitotically but cytokinesis is incomplete so oogonia remain connected in germ cell cysts. Oogonia begin to enter meiosis at 13.5 days postcoitum in the mouse and over several days, oocytes progress through the stages of meiotic prophase I arresting in the diplotene stage. Concurrently, germ cell cysts break apart and individual oocytes become surrounded by granulosa cells forming primordial follicles. In rats, inhibition of a synaptonemal complex protein caused premature arrival at the diplotene stage and premature primordial follicle assembly suggesting diplotene arrest might trigger primordial follicle formation. Cyst breakdown and primordial follicle formation are blocked by exposure to steroid hormones but hormone effects on the timing of diplotene arrest are unclear. Here, we asked: (1) if oocytes were required to arrest in diplotene before follicles formed, (2) if all oocytes within a germ cell cyst arrested at diplotene synchronously, and (3) if steroid hormones affected progression through prophase I. Meiotic stage and follicle formation were assessed in histological sections. Statistical differences over time were determined using one-way ANOVA followed by Newman-Keuls multiple comparisons test. To determine if steroid hormones affect the rate of progression to the diplotene stage, 17.5 dpc ovaries were placed in organ culture with media containing estradiol, progesterone or both hormones. In this case, differences were determined using one-way ANOVA followed by Dunnett's multiple comparisons test. We found primordial follicles containing oocytes at the diplotene stage as well as follicles containing oocytes at pre-diplotene stages. We also found individual germ cell cysts containing oocytes at both diplotene and pre-diplotene stages. Progesterone but not estradiol reduced the number of diplotene oocytes in ovary organ culture. Our results suggest that meiotic progression and primordial follicle formation are independent events. In addition, oocytes in germ cell cysts do not synchronously proceed through meiosis. Finally, only progesterone delayed transit though meiotic prophase I.////////////////// Knockdown of Progesterone Receptor (PGR) In Macaque Granulosa Cells Disrupts Ovulation and Progesterone Production. Bishop CV et al. (2016) Adenoviral vectors (vectors) expressing short-hairpin RNAs (shRNA) complementary to macaque nuclear progesterone receptor PGR mRNA (shPGR) or a non-targeting scrambled control (shScram) were used to determine the role PGR plays in ovulation/luteinization in rhesus monkeys. Nonluteinized granulosa cells (NLGCs) collected from monkeys (n=4) undergoing controlled ovarian stimulation protocols were exposed to either shPGR, shScram, or no virus for 24 h; hCG was then added to half of the wells to induce luteinization (LGCs; n=4-6 wells/treatment/monkey). Cells/media were collected 48, 72 and 120 h post-vector for evaluation of PGR mRNA and progesterone (P) levels. Addition of hCG increased (P< 0.05) PGR mRNA and media P levels in controls. However, a time-dependent decline (P < 0.05) in PGR mRNA and P occurred in shPGR vector groups. Injection of shPGR, but not shScram, vector into the preovulatory follicle 20 h before hCG administration during controlled ovulation (COv) protocols prevented follicle rupture in 5 of 6 monkeys as determined by laparoscopic evaluation; with a trapped oocyte confirmed in 3 of 4 follicles of excised ovaries. Injection of shPGR also prevented the rise in serum P levels following the hCG bolus compared to shScram (P < 0.05). Nuclear PGR immunostaining was undetectable in GCs from shPGR-injected follicles, compared to intense staining in shScram controls. Thus, the nuclear PGR appears to mediate P action in the dominant follicle promoting ovulation in primates. In vitro and in vivo effects of PGR knockdown in LGCs also support the hypothesis that P enhances its own synthesis in the primate corpus luteum by promoting luteinization.////////////////// Progesterone Plays a Critical Role in Canine Oocyte Maturation and Fertilization. Reynaud K et al. (2015) Canine oocyte maturation and fertilization take place within the oviducts under increasing plasma levels of progesterone (P4). In order to investigate the role of P4 in these processes, 51 Beagle bitches were treated with the P4 receptor antagonist aglepristone at the end of proestrus and 32 females were kept untreated. Fifteen treated and 13 control bitches were inseminated at Days +1 and +2 after ovulation (Day 0). Stages of oocyte maturation and embryo development were determined after ovariectomy at different time points after ovulation. Aglepristone did not prevent ovulation but delayed the resumption of oocyte meiosis and inhibited its progression: first metaphase (M) I stages were observed at 173 h post-ovulation and 39% of oocytes reached MII as late as 335 h post-ovulation in treated females whereas first MI occurred at 76 h and 100% of oocytes were in MII at 109 h post-ovulation in controls. Aglepristone extended the stay of morphologically normal oocytes within the oviducts: first signs of oocyte degeneration were observed at 335 h in treated vs. 100-110 h post-ovulation in control bitches. In inseminated females, aglepristone prevented sperm progression toward the oviducts and fertilization, although motile spermatozoa were observed in the uterine tip flush and within the cranial uterine glands. A proteomic analysis of the tubal fluid from treated and control non inseminated bitches at Day +4 evidenced 79 differential proteins potentially involved in the oocyte phenotype. In conclusion, P4 plays key roles in post-ovulatory canine oocyte maturation, aging and in fertilization.////////////////// Progesterone antagonist, RU486, represses LHCGR expression and LH/hCG signaling in cultured luteinized human mural granulosa cells. Yung Y 2013 et al. Abstract Progesterone, the main steroid synthesized by the corpus luteum (CL), prepares the uterus for implantation, maintains the CL survival, and induces progesterone auto-secretion. However, the molecular mechanisms involving the progesterone auto-secretion pathways at the luteal phase are not fully understood, especially in humans. We aim to study the molecular mechanism of the progesterone pathway in human granulosa cells. Our model system consists of luteinized human-mural-granulosa-cells (hmGCs) obtained from follicles aspirated during in vitro fertilization (IVF) procedures. hmGCs were seeded in culture and were subjected to different hormonal treatments. mRNA levels were analyzed by quantitative real-time PCR (qRT-PCR). Progesterone levels were measured by enzyme immunoassay (EIA). We show that exposure of luteinized hmGCs to the progesterone receptor antagonist, RU486 (mifepristone), resulted in inhibition of LHCGR, LH/hCG target genes and progesterone secretion. Exposure of hmGCs to medium that was incubated with hmGCs for 4?d - conditioned medium (CM), which contain 150??7.5?nM progesterone, resulted in induction of LHCGR and LH/hCG target genes, which was blocked by RU486. In addition, RU486 inhibited some of the progesterone biosynthesis pathway genes. Our results revealed a novel mechanism of the progesterone antagonist pathway in the luteal granulosa cells and emphasis the fundamental role of progesterone in the early luteal phase. ///////////////////////// Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Brache V et al. BACKGROUND Current methods of hormonal emergency contraception (EC) are ineffective in preventing follicular rupture when administered in the advanced pre-ovulatory phase. This study was designed to determine the capacity of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for EC, to block follicular rupture when administered with a follicle of >/=18 mm. Thirty-five women contributed with UPA (30 mg. oral) and a placebo cycle. Serial blood sampling for luteinizing hormone (LH), estradiol and progesterone measurements and follicular monitoring by ultrasound were performed before and for 5 days following treatment. Follicular rupture inhibition was assessed in the overall study population and in subgroups of women stratified by when treatment was administered in relation to LH levels (before the onset of the LH surge, after the onset of the surge but before the LH peak or after the LH peak. RESULTS Follicular rupture failed to occur for at least 5 days following UPA administration in 20/34 cycles , whereas rupture took place in all cycles within 5 days of placebo intake. When UPA was administered before the onset of the LH surge, or after the onset but before the LH peak, follicle rupture had not occurred within 5 days in 8/8 and 11/14 cycles, respectively. In contrast, when UPA was given after the LH peak, follicle rupture inhibition was only observed in 1/12 cycles. CONCLUSIONS This study demonstrates that UPA can significantly delay follicular rupture when given immediately before ovulation. This new generation EC compound could possibly prevent pregnancy when administered in the advanced follicular phase, even if LH levels have already begun to rise, a time when levonorgestrel EC is no longer effective in inhibiting ovulation. Progesterone receptor in the rat ovary: further characterization and localization in the granulosa cell. Schreiber JR et al. We have recently described a progesterone receptor in the cytosol of ovaries of hypophysectomized, estrogen-primed, immature rats. This progesterone receptor was shown to be a thermolabile, saturable protein, which is specific for progestins (R5020 and progesterone), and elutes at the void volume of a Sephadex G-200 column. In the present study, we performed a more detailed analysis of the biochemical properties of this receptor and examined its cellular localization within the ovary. Treatment of the ovary cytosol with protamine sulfate and N-ethyl maleimide abolishes the specific binding of 3H-R5020, indicating that the receptor is an acidic protein containing cysteine residues necessary for binding. Gel exclusion chromatography shows the progesterone receptor to have a mean Stokes radius of 86 A and a molecular weight of approximately 300,000 daltons. Kinetic analysis indicates that the receptor--R5020 complex dissociates very rapidly, with a t1/2 of 10 minutes. The cytosol of isolated granulosa cells bind 3H-R5020 specifically, demonstrating that the ovarian progesterone receptor is present in the granulosa cell. There has been mounting evidence indicating that PRs are an essential component of the ovulatory process. The observation that PR-/- knockout mice are incapable of undergoing ovulation, even in response to gonadotropin challenge, further supports the previous physiological evidence indicating that PRs in preovulatory follicles are induced before, and are necessary for, ovulation (Pinter et al., 1996). Recent evidence suggests that progesterone is required for ovulation, luteinization, and the maintenance of luteal structure and function in primates. Progesterone action is mediated by intracellular progesterone receptors (PRs) (Duffy et al., 1997. Rueda BR et al reported that decreased progesterone levels and progesterone receptor antagonists promote apoptotic cell death in bovine luteal cells.. Makrigiannakis A, 2000 reported that progesterone is an autocrine/paracrine regulator of human granulosa cell (GC) survival in vitro Human GC were isolated from follicular aspirates of women undergoing in vitro fertilization. GC were then cultured for 24 hours in serum-free media supplemented with progesterone and/or the progesterone antagonist RU486 and dexamethasone. Cells were then fixed and assessed for apoptosis by in situ end labeling of DNA fragments, cell cycle analysis of DNA content, and electron microscopy, When compared with controls, progesterone reduced and RU486 (an antiproesterone) increased the percentage of apoptotic GC, whereas dexamethasone had no effect. In addition, RU486 inhibited the protective effect of progesterone on GC survival . Taken together, these data indicate that progesterone inhibits human GC apoptosis, and this effect is mediated through the progesterone receptor. Rung E, et al 2004 reported that progesterone Receptor Antagonists and Statins Decrease De Novo Cholesterol Synthesis and Increase Apoptosis in Rat and Human Periovulatory Granulosa Cells In Vitro. Progesterone receptor (PR) stimulation promotes survival in rat and human periovulatory granulosa cells. To investigate the mechanisms involved, periovulatory rat granulosa cells were incubated in vitro with or without the PR antagonist Org 31710. Org 31710 caused the expected increase in apoptosis, and expression profiling using cDNA microarray revealed regulation of several groups of genes with functional and/or metabolic connections. This regulation included decreased expression of genes involved in follicular rupture, increased stress responses, decreased angiogenesis and decreased cholesterol synthesis. A decreased cholesterol synthesis was verified in experiments with both rat and human periovulatory granulosa cells treated with the PR antagonists Org 31710 or RU 486 by measuring incorporation of (14)C-acetate into cholesterol, cholesterol ester and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory rat granulosa cells using HMG-CoA reductase inhibitors (lovastatin, mevastatin or simvastatin) increased apoptosis, measured as DNA fragmentation and caspase-3/-7 activity. The increase in apoptosis caused by simvastatin was reversed by addition of the cholesterol synthesis intermediary mevalonic acid. These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival. Dominant Role of Nuclear Progesterone Receptor in the Control of Rat Periovulatory Granulosa Cell Apoptosis. Friberg PA et al. In this study, it was hypothesized that progesterone acts as a survival factor primarily by actions of the classical nuclear progesterone receptor (PGR) signaling pathway in rat periovulatory granulosa cells. Granulosa cells were isolated from immature female rats primed with eCG/hCG and treated in vitro with PGR antagonists. As little as 10 nanomolar of two different PGR antagonists (Org 31710 and RU 486) increased apoptosis measured as caspase 3/7 activity, which was reversed by co-treatment with the progestin R5020. Concurrently, progesterone synthesis was decreased. Inhibition of progesterone synthesis by cyanoketone similarly induced apoptosis but required a greater inhibition of progesterone synthesis than seen after treatment with PGR antagonists. Therefore, the induction of apoptosis by PGR antagonists cannot be explained by decreased progesterone synthesis alone. Low concentrations of R5020 also completely reversed the effects of cyanoketone. Inhibition of progesterone synthesis was more effective in inducing apoptosis than treatment with PGR antagonists. However, co-treatment with PGR antagonists protected the cells from the additional effects of cyanoketone, indicating partial agonist effects of the antagonists and a dominating role for the PGR in progesterone-mediated regulation of apoptosis. The progesterone receptor membrane component 1 (PGRMC1) was expressed in granulosa cells; however, an anti-PGRMC1 antibody did not induce apoptosis in periovulatory granulosa cells. Neither anti-PGRMC1 nor progesterone or cyanoketone affected apoptosis of immature granulosa cells. In conclusion, we show that progesterone regulates apoptosis in periovulatory granulosa cells by acting via the classical nuclear receptor. | ||||
| Expression regulated by | FSH, LH, Steroids | ||||
| Comment | Gonadotropin-induced expression of mRNA for cyclooxygenase-2 (COX-2) and production of prostaglandins E and F2{alpha} in bovine preovulatory follicles are regulated by the progesterone receptor. Bridges PJ et al. Follicular production of prostaglandins (PGs) is essential for ovulation, but the factors mediating gonadotropin-induced secretion of PGE and PGF2alpha remain largely unknown. We tested the hypothesis that gonadotropin-induced changes in progesterone and its receptor (PR) mediate the increase in periovulatory PGs. Heifers were treated with PGF2alpha and GnRH to induce luteolysis and the LH/FSH surge (ovulation occurs approximately 30 h post-GnRH). Since there are two increases in intrafollicular progesterone/PR mRNA during the bovine periovulatory period, we first examined the temporal pattern of PG production by follicles collected at 0, 3.5, 6, 12, 18, and 24 h post-GnRH. Although PGs did not increase in the follicular fluid until 24 h post-GnRH, acute secretion of PGs by follicle wall (theca + granulosa cells) was initiated by 18 h and had increased many-fold by 24 h post-GnRH. In vitro, FSH and LH induced dramatic transient increases in PG production by follicle wall and granulosa, but not theca, cells isolated from preovulatory follicles (0 h post-GnRH). PG accumulation peaked on day 2 of culture, mimicking the secretion pattern following a gonadotropin surge in vivo. In cultures of follicle wall and granulosa cells, the PR antagonist mifepristone (MIFE, 1 microM) inhibited LH-induced PG secretion and the progestin medroxyprogesterone acetate (MPA, 1 or 10 microM), but not the glucocorticoid dexamethasone (1 or 10 microM), overcame the effect of MIFE on PGs. Semi-quantitative RT-PCR revealed that MIFE inhibited LH-induced expression of COX-2 mRNA in granulosa cells in vitro. Again, treatment with MPA overcame the effect of MIFE. Together, these results provide strong evidence that periovulatory increases in COX-2 mRNA, PGE, and PGF2alpha are mediated by gonadotropin-induced increases in progesterone/PR, indicating that in some species there is an important functional relationship between these pathways in the ovulatory cascade. Ovarian progesterone production is stimulated by FSH and LH. Concomitant treatment with a synthetic progestin, R5020, (10(-6)M) increases the FSH-stimulated production of progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) in cultured rat granulosa cells. Likewise, R5020 augments the LH-stimulated progestin production in FSH-primed cells. Furthermore, the FSH stimulation of pregnenolone biosynthesis is enhanced by 10(-6) M of progesterone or R5020. These in vitro findings suggest that progestins may exert an autoregulatory positive feedback action to enhance gonadotropin-stimulated production of progesterone and 20 alpha-OH-P (Fanjul et al., 1983). Clemens et al reported induction of PR mRNA depends on the differentiation of granulosa cells in response to estrogen and a physiological amount of FSH followed by exposure to agonists (elevated levels of LH, FSH, and forskolin) that markedly increase cAMP. The activation of the A-kinase pathway leads to the phosphorylation of some transcription factor(s) other than or in addition to ER that is (are) critical for the transactivation of the PR gene and that this mechanism is selectively activated in differentiated granulosa cells possessing a preovulatory phenotype. | ||||
| Ovarian localization | Cumulus, Granulosa, Theca, Luteal cells, Large luteal cells | ||||
| Comment | PR was immunolocalized in 50 normal cycling human ovaries, and the relationship between these findings and the cellular localization of steroidogenic enzymes was examined. In the corpus luteum, in the period from ovulation to the mid-secretory phase, PR immunoreactivity was observed in a large number of both the luteinized granulosa and the theca cells Suzuki et al., 1994 . Immunohistochemistry also revealed that PR protein was present in both large and small luteal cellsRueda BR et al . | ||||
| Follicle stages | Antral, Preovulatory, Corpus luteum | ||||
| Comment | Control of Ovulation in Mice by Progesterone Receptor-Regulated Gene Networks. Kim J et al. The mid-cycle surge of luteinizing hormone (LH) induces ovulation, a process during which a fertilizable oocyte is released from a mature ovarian follicle. Although ovulation is a physiologically-well-characterized event, the underlying molecular pathways remain poorly understood. Progesterone receptor (PGR), which mediates the biological effects of the steroid hormone progesterone, has emerged as a key regulator of ovulation in mice. The development of a progesterone-receptor-null (Pgr-null) mouse model confirmed a critical role of this hormone in ovulation because in these mutant mice mature preovulatory follicles fail to release the oocytes (Lydon et al., 1995). This animal model has thus presented a unique opportunity to study the molecular pathways underlying ovulation. Gene-expression profiling experiments by several groups, using the ovaries of Pgr-null mice, revealed novel gene networks, which act downstream of PGR to control ovulation. These genes encode diverse molecules such as proteases, transcription factors, cell-adhesion molecules, modulators of vascular activities, and regulators of inflammation. Functional analyses using gene-knockout mouse models have confirmed that some of these factors play critical roles during ovulation. The knowledge gained from these studies has helped us to understand better the molecular mechanisms that facilitate the release of oocytes from preovulatory follicles. Further analysis of the role of molecular regulators of ovulation will help identify useful molecular targets that would allow the development of improved contraceptives and new therapeutics for anovulatory infertility. | ||||
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4 mutations
Species: mouse
Species: mouse
Species: human
Species: mouse
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