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Control of oocyte release by progesterone receptor-regulated gene expression.

Robker RL, Akison LK, Russell DL - Nucl Recept Signal (2009)

Bottom Line: The cellular mechanisms by which PGR regulates ovulation are currently under investigation, with several downstream pathways having been identified as PGR-regulated and potentially involved in follicular rupture.Interestingly, none of these PGR-regulated genes has been demonstrated to be a direct transcriptional target of PGR.Rather, in ovarian granulosa cells, PGR may act as an inducible coregulator for constitutively bound Sp1/Sp3 transcription factors, which are key regulators for a discrete cohort of ovulatory genes.

View Article: PubMed Central - PubMed

Affiliation: The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, SA, Australia. rebecca.robker@adelaide.edu.au

ABSTRACT
The progesterone receptor (PGR) is a nuclear receptor transcription factor that is essential for female fertility, in part due to its control of oocyte release from the ovary, or ovulation. In all mammals studied to date, ovarian expression of PGR is restricted primarily to granulosa cells of follicles destined to ovulate. Granulosa cell expression of PGR is induced by the pituitary Luteinizing Hormone (LH) surge via mechanisms that are not entirely understood, but which involve activation of Protein Kinase A and modification of Sp1/Sp3 transcription factors on the PGR promoter. Null mutations for PGR or treatment with PGR antagonists block ovulation in all species analyzed, including humans. The cellular mechanisms by which PGR regulates ovulation are currently under investigation, with several downstream pathways having been identified as PGR-regulated and potentially involved in follicular rupture. Interestingly, none of these PGR-regulated genes has been demonstrated to be a direct transcriptional target of PGR. Rather, in ovarian granulosa cells, PGR may act as an inducible coregulator for constitutively bound Sp1/Sp3 transcription factors, which are key regulators for a discrete cohort of ovulatory genes.

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Progesterone receptor (PGR) is expressed in the ovary in a temporal and cell-type specific manner, as demonstrated by PRlacZ mice, which express the lacZ reporter (blue) under the control of the endogenous PGR promoter.Top panels: Ovaries from mice treated with PMSG do not express PGR, while the oviduct expresses high levels.  Middle panels: In response to hCG to mimic the LH surge, lacZ staining is detected within 8h, specifically in the granulosa cells of preovulatory follicles.  Lower panel: In preovulatory follicles, lacZ is detected in mural granulosa cells (blue arrow), but not cumulus cells (black arrow) or the oocyte (O). (Reprinted with permission from Ismail et al., 2002).  Copyright 2002, The Endocrine Society.
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fig2: Progesterone receptor (PGR) is expressed in the ovary in a temporal and cell-type specific manner, as demonstrated by PRlacZ mice, which express the lacZ reporter (blue) under the control of the endogenous PGR promoter.Top panels: Ovaries from mice treated with PMSG do not express PGR, while the oviduct expresses high levels. Middle panels: In response to hCG to mimic the LH surge, lacZ staining is detected within 8h, specifically in the granulosa cells of preovulatory follicles. Lower panel: In preovulatory follicles, lacZ is detected in mural granulosa cells (blue arrow), but not cumulus cells (black arrow) or the oocyte (O). (Reprinted with permission from Ismail et al., 2002). Copyright 2002, The Endocrine Society.

Mentions: PGR mRNA and protein isoforms are expressed in a temporally and cell-type restricted manner in the ovary. PGR mRNA is rapidly yet transiently induced in the rat ovary in vivo [Park and Mayo, 1991] and in primary cultures of rat granulosa cells, peaking after 4-8h in response to LH [Clemens et al., 1998; Natraj and Richards, 1993]. PGR mRNA expression has not been directly localized in the mouse, but the PRlacZ mouse model, whereby the lacZ reporter was placed within exon 1 of the PGR gene, demonstrates that PGR is expressed within 4h of the LH surge, specifically in mural granulosa cells (Figure 2) [Ismail et al., 2002]. PGR protein has also been localized to granulosa cells of mouse preovulatory follicles, transiently up-regulated at 4h and 8h post-hCG [Robker et al., 2000] and undetectable by 12h. Consistent with differences in LH-R expression, PGR is expressed at dramatically higher levels in mural granulosa cells than in cumulus cells (Figure 2) [Ismail et al., 2002; Robker et al., 2000; Teilmann et al., 2006].


Control of oocyte release by progesterone receptor-regulated gene expression.

Robker RL, Akison LK, Russell DL - Nucl Recept Signal (2009)

Progesterone receptor (PGR) is expressed in the ovary in a temporal and cell-type specific manner, as demonstrated by PRlacZ mice, which express the lacZ reporter (blue) under the control of the endogenous PGR promoter.Top panels: Ovaries from mice treated with PMSG do not express PGR, while the oviduct expresses high levels.  Middle panels: In response to hCG to mimic the LH surge, lacZ staining is detected within 8h, specifically in the granulosa cells of preovulatory follicles.  Lower panel: In preovulatory follicles, lacZ is detected in mural granulosa cells (blue arrow), but not cumulus cells (black arrow) or the oocyte (O). (Reprinted with permission from Ismail et al., 2002).  Copyright 2002, The Endocrine Society.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2807638&req=5

fig2: Progesterone receptor (PGR) is expressed in the ovary in a temporal and cell-type specific manner, as demonstrated by PRlacZ mice, which express the lacZ reporter (blue) under the control of the endogenous PGR promoter.Top panels: Ovaries from mice treated with PMSG do not express PGR, while the oviduct expresses high levels. Middle panels: In response to hCG to mimic the LH surge, lacZ staining is detected within 8h, specifically in the granulosa cells of preovulatory follicles. Lower panel: In preovulatory follicles, lacZ is detected in mural granulosa cells (blue arrow), but not cumulus cells (black arrow) or the oocyte (O). (Reprinted with permission from Ismail et al., 2002). Copyright 2002, The Endocrine Society.
Mentions: PGR mRNA and protein isoforms are expressed in a temporally and cell-type restricted manner in the ovary. PGR mRNA is rapidly yet transiently induced in the rat ovary in vivo [Park and Mayo, 1991] and in primary cultures of rat granulosa cells, peaking after 4-8h in response to LH [Clemens et al., 1998; Natraj and Richards, 1993]. PGR mRNA expression has not been directly localized in the mouse, but the PRlacZ mouse model, whereby the lacZ reporter was placed within exon 1 of the PGR gene, demonstrates that PGR is expressed within 4h of the LH surge, specifically in mural granulosa cells (Figure 2) [Ismail et al., 2002]. PGR protein has also been localized to granulosa cells of mouse preovulatory follicles, transiently up-regulated at 4h and 8h post-hCG [Robker et al., 2000] and undetectable by 12h. Consistent with differences in LH-R expression, PGR is expressed at dramatically higher levels in mural granulosa cells than in cumulus cells (Figure 2) [Ismail et al., 2002; Robker et al., 2000; Teilmann et al., 2006].

Bottom Line: The cellular mechanisms by which PGR regulates ovulation are currently under investigation, with several downstream pathways having been identified as PGR-regulated and potentially involved in follicular rupture.Interestingly, none of these PGR-regulated genes has been demonstrated to be a direct transcriptional target of PGR.Rather, in ovarian granulosa cells, PGR may act as an inducible coregulator for constitutively bound Sp1/Sp3 transcription factors, which are key regulators for a discrete cohort of ovulatory genes.

View Article: PubMed Central - PubMed

Affiliation: The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, SA, Australia. rebecca.robker@adelaide.edu.au

ABSTRACT
The progesterone receptor (PGR) is a nuclear receptor transcription factor that is essential for female fertility, in part due to its control of oocyte release from the ovary, or ovulation. In all mammals studied to date, ovarian expression of PGR is restricted primarily to granulosa cells of follicles destined to ovulate. Granulosa cell expression of PGR is induced by the pituitary Luteinizing Hormone (LH) surge via mechanisms that are not entirely understood, but which involve activation of Protein Kinase A and modification of Sp1/Sp3 transcription factors on the PGR promoter. Null mutations for PGR or treatment with PGR antagonists block ovulation in all species analyzed, including humans. The cellular mechanisms by which PGR regulates ovulation are currently under investigation, with several downstream pathways having been identified as PGR-regulated and potentially involved in follicular rupture. Interestingly, none of these PGR-regulated genes has been demonstrated to be a direct transcriptional target of PGR. Rather, in ovarian granulosa cells, PGR may act as an inducible coregulator for constitutively bound Sp1/Sp3 transcription factors, which are key regulators for a discrete cohort of ovulatory genes.

Show MeSH
Related in: MedlinePlus