Control of oocyte release by progesterone receptor-regulated gene expression

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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Faculty Opinions recommendation of A new class of transcription factors mediates brassinosteroid-regulated gene expression in Arabidopsis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1024000.285829 ◽

2005 ◽

Author(s):

Xing Wang Deng

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

New Class ◽

Regulated Gene Expression

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Hormone Induction of Progesterone Receptor (PR) Messenger Ribonucleic Acid and Activation of PR Promoter Regions in Ovarian Granulosa Cells: Evidence for a Role of Cyclic Adenosine 3′,5′-Monophosphate but Not Estradiol

Molecular Endocrinology ◽

10.1210/mend.12.8.0157 ◽

1998 ◽

Vol 12 (8) ◽

pp. 1201-1214 ◽

Cited By ~ 1

Author(s):

Jeffrey W. Clemens ◽

Rebecca L. Robker ◽

W. Lee Kraus ◽

Benita S. Katzenellenbogen ◽

JoAnne S. Richards

Keyword(s):

Progesterone Receptor ◽

Granulosa Cells ◽

Ribonucleic Acid ◽

Promoter Regions ◽

Messenger Ribonucleic Acid ◽

Ovarian Granulosa Cells

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Cellular adaptation to hypoxia: O 2 ‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O 2 ‐regulated gene expression

The FASEB Journal ◽

10.1096/fj.01-0944rev ◽

2002 ◽

Vol 16 (10) ◽

pp. 1151-1162 ◽

Cited By ~ 774

Author(s):

Roland H. Wenger

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Adaptation To Hypoxia ◽

Cellular Adaptation ◽

Regulated Gene Expression

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Progesterone receptor A-regulated gene expression in mammary organoid cultures

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2009.04.001 ◽

2009 ◽

Vol 115 (3-5) ◽

pp. 161-172 ◽

Cited By ~ 25

Author(s):

Sarah J. Santos ◽

Mark D. Aupperlee ◽

Jianwei Xie ◽

Srinivasan Durairaj ◽

Richard Miksicek ◽

...

Keyword(s):

Gene Expression ◽

Progesterone Receptor ◽

Organoid Cultures ◽

Regulated Gene Expression

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Disrupting effects of bifenthrin on ovulatory gene expression and prostaglandin synthesis in rat ovarian granulosa cells

Toxicology ◽

10.1016/j.tox.2011.01.007 ◽

2011 ◽

Vol 282 (1-2) ◽

pp. 47-55 ◽

Cited By ~ 44

Author(s):

Jing Liu ◽

Ye Yang ◽

Yan Yang ◽

Ying Zhang ◽

Weiping Liu

Keyword(s):

Gene Expression ◽

Granulosa Cells ◽

Prostaglandin Synthesis ◽

Ovarian Granulosa Cells

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Involvement of Cyclic Adenosine 5′-Monophosphate Response Element-Binding Protein, Steroidogenic Factor 1, and Dax-1 in the Regulation of Gonadotropin-Inducible Ovarian Transcription Factor 1 Gene Expression by Follicle-Stimulating Hormone in Ovarian Granulosa Cells

Endocrinology ◽

10.1210/en.2002-221070 ◽

2003 ◽

Vol 144 (5) ◽

pp. 1920-1930 ◽

Cited By ~ 40

Author(s):

Takashi Yazawa ◽

Tetsuya Mizutani ◽

Kazuya Yamada ◽

Hiroko Kawata ◽

Toshio Sekiguchi ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Granulosa Cells ◽

Binding Protein ◽

Follicle Stimulating Hormone ◽

Response Element ◽

Steroidogenic Factor 1 ◽

Ovarian Granulosa Cells ◽

Element Binding Protein ◽

Transcription Factor 1

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Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles

Reproduction ◽

10.1530/rep-08-0457 ◽

2009 ◽

Vol 137 (5) ◽

pp. 843-855 ◽

Cited By ~ 51

Author(s):

Martha Z Carletti ◽

Lane K Christenson

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Cell Signaling ◽

Granulosa Cell ◽

Granulosa Cells ◽

Egf Receptor ◽

Cell Function ◽

Early Response ◽

Cell Gene Expression

LH acts on periovulatory granulosa cells by activating the PKA pathway as well as other cell signaling cascades to increase the transcription of specific genes necessary for ovulation and luteinization. Collectively, these cell signaling responses occur rapidly (within minutes); however, presently no high throughput studies have reported changes before 4 h after the LH surge. To identify early response genes that are likely critical for initiation of ovulation and luteinization, mouse granulosa cells were collected before and 1 h after hCG. Fifty-seven gene transcripts were significantly (P<0.05) upregulated and three downregulated following hCG. Twenty-four of these transcripts were known to be expressed after the LH/hCG surge at later time points, while 36 were unknown to be expressed by periovulatory granulosa cells. Temporal expression of several transcripts, including the transcription factorsNr4a1,Nr4a2,Egr1,Egr2,Btg1, andBtg2, and the epidermal growth factor (EGF)-like ligandsAregandEreg, were analyzed by quantitative RT-PCR, and their putative roles in granulosa cell function are discussed. Epigen (Epgn), another member of the family of EGF-like ligands was identified for the first time in granulosa cells as rapidly induced by LH/hCG. We demonstrate thatEpgninitiates cumulus expansion, similar to the other EGF-receptor ligandsAregandEreg. These studies illustrate that a number of changes in gene expression occurin vivoin response to LH, and that many of the differentially expressed genes are transcription factors that we would predict in turn modulate granulosa cell gene expression to ultimately impact the processes of ovulation and luteinization.

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