NCBI Summary:
The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple alternatively spliced transcript variants encoding eight distinct isoforms have been reported.
Use of heterologous complementary DNA array screening to analyze bovine oocyte transcriptome and its evolution during in vitro maturation. Dalbi?Tran R et al. We have analyzed gene expression in bovine oocytes before and after in vitro maturation (IVM) using heterologous hybridization onto cDNA array. Total RNA was purified from pools of over 200 oocytes either immediately after aspiration from follicles at the surface of slaughterhouse cow ovaries or following in vitro maturation. Radiolabeled cDNA probes were generated by reverse-transcription followed by linear PCR amplification and were hybridized to Atlas human cDNA arrays. To our knowledge, this is the first report of gene expression profiling by this technology in the mammalian female germ cell. Our results demonstrate that cDNA array screening is a suitable method for analyzing the transcription pattern in oocytes. About 300 identified genes were reproducibly shown to be expressed in the bovine oocyte, the largest profile available so far in this model. The relative abundance of most messenger RNAs appeared stable during IVM. However, 70 transcripts underwent a significant differential regulation (by a factor of at least two). Their potential role in the context of oocyte maturation is discussed. Together they constitute a molecular signature of the degree of oocyte cytoplasmic maturation achieved in vitro.
Expression regulated by
LH
Comment
Primate Granulosa Cell Response via Prostaglandin E2 Receptors Increases Late in the Periovulatory Interval. Markosyan N et al. Successful ovulation requires elevated follicular PGE2 levels. To determine which PGE2 receptors are available to mediate periovulatory events in follicles, granulosa cells and whole ovaries were collected from monkeys before (0 hour (h)) and after administration of an ovulatory dose of hCG to span the 40 h periovulatory interval. All PGE2 receptor mRNAs were present in monkey granulosa cells. As assessed by immunofluorescence, PTGER1 (EP1) protein was low/nondetectable in granulosa cells 0, 12, and 24 h after hCG but was abundant 36 h after hCG administration. PTGER2 (EP2) and PTGER3 (EP3) proteins were detected by immunofluorescence in granulosa cells throughout the periovulatory interval, and western blotting showed an increase in PTGER2 and PTGER3 levels between 0 and 36 h after hCG. In contrast, PTGER4 (EP4) protein was not detected in monkey granulosa cells. Granulosa cell response to PGE2 receptor agonists was examined 24 h and 36 h after hCG administration, when elevated PGE2 levels present in periovulatory follicles initiate ovulatory events. PGE2 acts via PTGER1 to increase intracellular calcium. PGE2 increased intracellular calcium in granulosa cells obtained 36 h (but not 24 h) after hCG; this effect of PGE2 was blocked by a PTGER1 antagonist. A PTGER2-specific agonist and a PTGER3-specific agonist each elevated cAMP in granulosa cells obtained 36 h (but not 24 h) after hCG. Therefore, granulosa cells of primate periovulatory follicles express multiple receptors for PGE2. Granulosa cells respond to agonist stimulation of each of these receptors 36 h, but not 24 h, after hCG, supporting the hypothesis that granulosa cells are most sensitive to PGE2 as follicular PGE2 levels peak, leading to maximal PGE2-mediated periovulatory effects just before ovulation.
Ovarian localization
Oocyte, Cumulus, Granulosa, Luteal cells
Comment
Prostaglandin E2 Receptors Are Differentially Expressed in Subpopulations of Granulosa Cells from Primate Periovulatory Follicles. Harris SM et al. Prostaglandin E2 (PGE2) mediates many effects of the mid-cycle LH surge within the periovulatory follicle. Differential expression of the four PGE2 (EP) receptors may contribute to the specialized functions of each granulosa cell subpopulation. To determine if EP receptors are differentially expressed in granulosa cells, monkeys received gonadotropins to stimulate ovarian follicular development. Periovulatory events were initiated with hCG; granulosa cells and whole ovaries were collected before (0 h) and after (24-36 h) hCG to span the 40-h primate periovulatory interval. EP receptor mRNA and protein levels were quantified in granulosa cell subpopulations. Cumulus cells expressed higher levels of EP2 and EP3 mRNA compared to mural cells 36 hours after hCG. Cumulus cell EP2 and EP3 protein levels also increased between 0 h and 36 h after hCG. Overall, mural granulosa cells expressed low levels of EP1 protein at 0 h and higher levels 24-36 h after hCG. However, EP1 protein levels were higher in granulosa cells away from the follicle apex when compared to apex cells 36 h after hCG. Higher levels of PAI-1 protein were measured in non-apex cells, consistent with a previous study showing EP1-stimulated PAI-1 protein expression in monkey granulosa cells. EP4 protein levels were low in all subpopulations. In summary, cumulus cells likely respond to PGE2 via EP2 and EP3, while PGE2 controls rupture of a specific region of the follicle via EP1. Therefore, differential expression of EP receptors may permit each granulosa cell subpopulation to generate a unique response to PGE2 during the process of ovulation.
The corpus luteum (CL) is a transient ovarian endocrine gland formed from the ovulated follicle. Progesterone (P4) is the primary secretory product of CL and essential for establishment of pregnancy in mammals. In the cyclic female, the life span of CL is characterized by luteal development, maintenance and regression regulated by complex interactions between luteotrophic and luteolytic mediators. It is universally accepted that PGF2a is the luteolysin while PGE2 is considered as a luteotropin in most mammals irrespective of origin either uterus and /or CL. New emerging concepts emphasize the autocrine and paracrine actions of luteal PGs in CL function. However, there is no report on selective biosynthesis and cellular transport of luteal PGE2 and PGF2alpha in the CL of any species. Arosh J et al 2004 have studied the expression of enzymes involved in the metabolism of PGE2 and PGF2alpha, cyclooxygenase (COX) 1 and 2, PG synthases (PGES and PGFS), prostaglandin 15-dehydrogenase (PGDH), and PG transporter (PGT) as well as receptors (EP2, EP3 and FP) throughout the CL life span using a bovine model. COX-1, PGFS and PGDH are expressed at constant levels whereas COX-2, PGES, PGT, EP2, EP3 and FP are highly modulated during different phases of the CL life span. The PG components are preferentially expressed in large luteal cells. The results indicate that PGE2 biosynthesis, transport and signaling cascades are selectively activated during luteal maintenance. By contrast PGF2alpha system is activated during luteal regression.
Follicle stages
Corpus luteum
Comment
Prostaglandin E2 Receptors Are Differentially Expressed in Subpopulations of Granulosa Cells from Primate Periovulatory Follicles. Harris SM et al. Prostaglandin E2 (PGE2) mediates many effects of the mid-cycle LH surge within the periovulatory follicle. Differential expression of the four PGE2 (EP) receptors may contribute to the specialized functions of each granulosa cell subpopulation. To determine if EP receptors are differentially expressed in granulosa cells, monkeys received gonadotropins to stimulate ovarian follicular development. Periovulatory events were initiated with hCG; granulosa cells and whole ovaries were collected before (0 h) and after (24-36 h) hCG to span the 40-h primate periovulatory interval. EP receptor mRNA and protein levels were quantified in granulosa cell subpopulations. Cumulus cells expressed higher levels of EP2 and EP3 mRNA compared to mural cells 36 hours after hCG. Cumulus cell EP2 and EP3 protein levels also increased between 0 h and 36 h after hCG. Overall, mural granulosa cells expressed low levels of EP1 protein at 0 h and higher levels 24-36 h after hCG. However, EP1 protein levels were higher in granulosa cells away from the follicle apex when compared to apex cells 36 h after hCG. Higher levels of PAI-1 protein were measured in non-apex cells, consistent with a previous study showing EP1-stimulated PAI-1 protein expression in monkey granulosa cells. EP4 protein levels were low in all subpopulations. In summary, cumulus cells likely respond to PGE2 via EP2 and EP3, while PGE2 controls rupture of a specific region of the follicle via EP1. Therefore, differential expression of EP receptors may permit each granulosa cell subpopulation to generate a unique response to PGE2 during the process of ovulation.