Rethinking progesterone regulation of female reproductive cyclicity

The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of ra...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 15; pp. 4212 - 4217
Main Authors Kubota, Kaiyu, Cui, Wei, Dhakal, Pramod, Wolfe, Michael W., Rumi, M. A. Karim, Vivian, Jay L., Roby, Katherine F., Soares, Michael J.
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LanguageEnglish
Published United States National Academy of Sciences 12.04.2016
National Acad Sciences
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Abstract The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null mutation at the Pgr locus has forced a reexamination of the role of progesterone in the regulation of the female reproductive cycle. We generated two Pgr mutant rat models, using genome editing. In both cases, deletions yielded a null mutation resulting from a nonsense frame-shift and the emergence of a stop codon. Similar to Pgr null mice, Pgr null rats were infertile because of deficits in sexual behavior, ovulation, and uterine endometrial differentiation. However, in contrast to the reported phenotype of female mice with disruptions in Pgr signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in vaginal cytology, uterine histology, serum hormone levels, and wheel running activity were evident in Pgr null female rats, similar to wild-type controls. Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild-type female rats but not in Pgr-null female rats. As previously reported, pharmacologic antagonism supports a role for PGR signaling in the regulation of the ovulatory gonadotropin surge, a result at variance with experimentation using genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat challenge current assumptions and prompt a reevaluation of the hormonal control of reproductive cyclicity.
AbstractList The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null mutation at the Pgr locus has forced a reexamination of the role of progesterone in the regulation of the female reproductive cycle. We generated two Pgr mutant rat models, using genome editing. In both cases, deletions yielded a null mutation resulting from a nonsense frame-shift and the emergence of a stop codon. Similar to Pgr null mice, Pgr null rats were infertile because of deficits in sexual behavior, ovulation, and uterine endometrial differentiation. However, in contrast to the reported phenotype of female mice with disruptions in Pgr signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in vaginal cytology, uterine histology, serum hormone levels, and wheel running activity were evident in Pgr null female rats, similar to wild-type controls. Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild-type female rats but not in Pgr-null female rats. As previously reported, pharmacologic antagonism supports a role for PGR signaling in the regulation of the ovulatory gonadotropin surge, a result at variance with experimentation using genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat challenge current assumptions and prompt a reevaluation of the hormonal control of reproductive cyclicity.
Progesterone possesses an essential role in regulating female fertility, with prominent actions throughout the female reproductive axis. The neuroendocrine actions of progesterone have been viewed as critical for the control of the female reproductive cycle. This basic principle has been reinforced by in vivo experimental paradigms, using hormone replacement as well as pharmacologic and genetic disruption of the progesterone receptor (PGR). Phenotypic characterization of Pgr null rats strengthens roles for progesterone in the regulation of female fertility, but not roles for progesterone as an essential determinant of female reproductive cyclicity, challenging an elemental principle of mammalian reproductive biology. Such findings demonstrate the benefits of genome editing in expanding available animal models for physiologic investigation. The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null mutation at the Pgr locus has forced a reexamination of the role of progesterone in the regulation of the female reproductive cycle. We generated two Pgr mutant rat models, using genome editing. In both cases, deletions yielded a null mutation resulting from a nonsense frame-shift and the emergence of a stop codon. Similar to Pgr null mice, Pgr null rats were infertile because of deficits in sexual behavior, ovulation, and uterine endometrial differentiation. However, in contrast to the reported phenotype of female mice with disruptions in Pgr signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in vaginal cytology, uterine histology, serum hormone levels, and wheel running activity were evident in Pgr null female rats, similar to wild-type controls. Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild-type female rats but not in Pgr -null female rats. As previously reported, pharmacologic antagonism supports a role for PGR signaling in the regulation of the ovulatory gonadotropin surge, a result at variance with experimentation using genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat challenge current assumptions and prompt a reevaluation of the hormonal control of reproductive cyclicity.
Author Cui, Wei
Dhakal, Pramod
Wolfe, Michael W.
Rumi, M. A. Karim
Soares, Michael J.
Roby, Katherine F.
Vivian, Jay L.
Kubota, Kaiyu
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  givenname: Wei
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  surname: Soares
  fullname: Soares, Michael J.
  organization: Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160
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Cites_doi 10.1210/endo.140.8.6895
10.1038/nprot.2014.171
10.1210/endo-107-5-1286
10.1530/rep.0.1250143
10.1159/000339822
10.1371/journal.pone.0029021
10.1210/en.2015-1397
10.1095/biolreprod35.5.1154
10.1210/endo-43-6-389
10.1210/endo-96-1-219
10.1073/pnas.95.18.10978
10.1210/en.2010-0440
10.1095/biolreprod29.3.630
10.3389/fnins.2013.00168
10.1210/en.2015-1300
10.1186/1480-9222-13-4
10.1101/gad.9.18.2266
10.1210/endo-72-2-305
10.1037/h0030242
10.1210/jcem-63-6-1270
10.1210/endo-82-1-193
10.1210/me.2002-0270
10.1095/biolreprod14.1.82
10.1095/biolreprod34.2.327
10.1016/0018-506X(74)90018-X
10.1038/ncb-nm-fertilityS41
10.1128/MCB.25.6.2406-2418.2005
10.1210/en.2005-0016
10.1152/physrev.1979.59.2.229
10.1210/endo-94-6-1704
10.1073/pnas.080073497
10.1006/frne.2001.0210
10.1016/0018-506X(71)90003-1
10.1210/endo.138.10.5456
10.1210/edrv-7-1-75
10.1210/edrv.20.3.0370
10.1007/978-1-60327-389-3_15
10.1007/978-1-4684-5101-6_21
10.1210/jcem-48-1-127
10.1196/annals.1429.018
10.1073/pnas.90.23.11162
10.1677/jme.1.02058
10.1073/pnas.122225699
10.1242/dev.127.19.4277
10.1210/endo.133.6.8243259
10.1095/biolreprod56.2.293
10.1210/rp.57.1.339
10.1177/0192623315570339
10.1016/j.contraception.2012.08.002
10.1016/j.cell.2015.04.052
10.1210/en.2013-2150
10.1210/en.2006-1561
10.1016/j.yfrne.2011.01.001
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Author contributions: K.K. and M.J.S. designed research; K.K., W.C., P.D., and K.F.R. performed research; M.A.K.R. and J.L.V. contributed new reagents/analytic tools; K.K., M.W.W., J.L.V., K.F.R., and M.J.S. analyzed data; and K.K. and M.J.S. wrote the paper.
Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved March 7, 2016 (received for review February 2, 2016)
2Present address: Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, MA 01003.
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References 3087144 - Adv Exp Med Biol. 1986;196:317-28
24506075 - Endocrinology. 2014 May;155(5):1991-9
3456802 - Biol Reprod. 1986 Mar;34(2):327-35
24065879 - Front Neurosci. 2013 Sep 19;7:168
5634993 - Endocrinology. 1968 Jan;82(1):193-5
26076042 - Endocrinology. 2015 Sep;156(9):3091-7
9724815 - Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10978-83
26046438 - Cell. 2015 Jun 4;161(6):1334-44
6414543 - Biol Reprod. 1983 Oct;29(3):630-6
22687885 - Neuroendocrinology. 2012;96(2):162-71
2681741 - J Reprod Fertil Suppl. 1989;37:253-60
18100247 - Endocrinology. 1948 Dec;43(6):389-405
10433223 - Endocrinology. 1999 Aug;140(8):3653-8
22272226 - PLoS One. 2012;7(1):e29021
25739587 - Toxicol Pathol. 2015 Aug;43(6):776-93
177109 - Biol Reprod. 1976 Feb;14(1):82-94
7000489 - Endocrinology. 1980 Nov;107(5):1286-90
26204463 - Endocrinology. 2015 Oct;156(10 ):3791-803
12456805 - Mol Endocrinol. 2002 Dec;16(12):2853-71
3097053 - J Clin Endocrinol Metab. 1986 Dec;63(6):1270-6
20660062 - Endocrinology. 2010 Sep;151(9):4537-50
15845616 - Endocrinology. 2005 Aug;146(8):3490-505
1167352 - Endocrinology. 1975 Jan;96(1):219-26
12479614 - Nat Cell Biol. 2002 Oct;4 Suppl:s41-9
9322923 - Endocrinology. 1997 Oct;138(10):4147-52
217888 - J Clin Endocrinol Metab. 1979 Jan;48(1):127-32
8243259 - Endocrinology. 1993 Dec;133(6):2418-23
10368776 - Endocr Rev. 1999 Jun;20(3):358-417
10976058 - Development. 2000 Oct;127(19):4277-91
7557380 - Genes Dev. 1995 Sep 15;9(18):2266-78
21663682 - Biol Proced Online. 2011 Jun 10;13(1):4
12578528 - Reproduction. 2003 Feb;125(2):143-9
22995540 - Contraception. 2013 Mar;87(3):319-30
12048256 - Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7940-4
108689 - Physiol Rev. 1979 Apr;59(2):229-84
5514672 - J Comp Physiol Psychol. 1970 Dec;73(3):349-58
9116124 - Biol Reprod. 1997 Feb;56(2):293-302
4455593 - Horm Behav. 1974 Dec;5(4):317-35
21216259 - Front Neuroendocrinol. 2011 Aug;32(3):367-75
3103699 - Biol Reprod. 1986 Dec;35(5):1154-61
20013236 - Methods Mol Biol. 2010;597:211-25
14025765 - Endocrinology. 1963 Feb;72:305-16
15743833 - Mol Cell Biol. 2005 Mar;25(6):2406-18
10781075 - Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4689-94
3082617 - Endocr Rev. 1986 Feb;7(1):75-88
25255092 - Nat Protoc. 2014 Oct;9(10):2493-512
8248223 - Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11162-6
17303655 - Endocrinology. 2007 May;148(5):2471-86
18574203 - Ann N Y Acad Sci. 2008;1135:10-8
4857496 - Endocrinology. 1974 Jun;94(6):1704-8
11259133 - Front Neuroendocrinol. 2001 Apr;22(2):69-106
12017551 - Recent Prog Horm Res. 2002;57:339-55
17242168 - J Mol Endocrinol. 2007 Feb;38(1-2):35-50
e_1_3_3_50_2
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References_xml – ident: e_1_3_3_20_2
  doi: 10.1210/endo.140.8.6895
– volume-title: Memoirs of the University of California
  year: 1922
  ident: e_1_3_3_12_2
  contributor:
    fullname: Long JA
– ident: e_1_3_3_46_2
  doi: 10.1038/nprot.2014.171
– ident: e_1_3_3_3_2
  doi: 10.1210/endo-107-5-1286
– ident: e_1_3_3_11_2
  doi: 10.1530/rep.0.1250143
– ident: e_1_3_3_23_2
  doi: 10.1159/000339822
– ident: e_1_3_3_39_2
  doi: 10.1371/journal.pone.0029021
– ident: e_1_3_3_49_2
  doi: 10.1210/en.2015-1397
– ident: e_1_3_3_26_2
  doi: 10.1095/biolreprod35.5.1154
– ident: e_1_3_3_13_2
  doi: 10.1210/endo-43-6-389
– ident: e_1_3_3_48_2
  doi: 10.1210/endo-96-1-219
– ident: e_1_3_3_31_2
  doi: 10.1073/pnas.95.18.10978
– ident: e_1_3_3_50_2
  doi: 10.1210/en.2010-0440
– ident: e_1_3_3_55_2
  doi: 10.1095/biolreprod29.3.630
– ident: e_1_3_3_24_2
  doi: 10.3389/fnins.2013.00168
– ident: e_1_3_3_30_2
  doi: 10.1210/en.2015-1300
– ident: e_1_3_3_56_2
  doi: 10.1186/1480-9222-13-4
– ident: e_1_3_3_7_2
  doi: 10.1101/gad.9.18.2266
– ident: e_1_3_3_52_2
  doi: 10.1210/endo-72-2-305
– ident: e_1_3_3_22_2
  doi: 10.1037/h0030242
– ident: e_1_3_3_25_2
  doi: 10.1210/jcem-63-6-1270
– ident: e_1_3_3_21_2
  doi: 10.1210/endo-82-1-193
– ident: e_1_3_3_40_2
  doi: 10.1210/me.2002-0270
– ident: e_1_3_3_14_2
  doi: 10.1095/biolreprod14.1.82
– ident: e_1_3_3_51_2
  doi: 10.1095/biolreprod34.2.327
– ident: e_1_3_3_54_2
  doi: 10.1016/0018-506X(74)90018-X
– ident: e_1_3_3_16_2
  doi: 10.1038/ncb-nm-fertilityS41
– ident: e_1_3_3_38_2
  doi: 10.1128/MCB.25.6.2406-2418.2005
– start-page: 31
  volume-title: Clinical Reproductive Medicine and Surgery: A Practical Guide
  year: 2012
  ident: e_1_3_3_2_2
  contributor:
    fullname: Beshay VE
– ident: e_1_3_3_41_2
  doi: 10.1210/en.2005-0016
– ident: e_1_3_3_34_2
  doi: 10.1152/physrev.1979.59.2.229
– ident: e_1_3_3_47_2
  doi: 10.1210/endo-94-6-1704
– ident: e_1_3_3_18_2
  doi: 10.1073/pnas.080073497
– ident: e_1_3_3_32_2
  doi: 10.1006/frne.2001.0210
– ident: e_1_3_3_53_2
  doi: 10.1016/0018-506X(71)90003-1
– ident: e_1_3_3_19_2
  doi: 10.1210/endo.138.10.5456
– ident: e_1_3_3_4_2
  doi: 10.1210/edrv-7-1-75
– ident: e_1_3_3_9_2
  doi: 10.1210/edrv.20.3.0370
– ident: e_1_3_3_45_2
  doi: 10.1007/978-1-60327-389-3_15
– ident: e_1_3_3_43_2
  doi: 10.1007/978-1-4684-5101-6_21
– ident: e_1_3_3_42_2
  doi: 10.1210/jcem-48-1-127
– ident: e_1_3_3_1_2
  doi: 10.1196/annals.1429.018
– ident: e_1_3_3_6_2
  doi: 10.1073/pnas.90.23.11162
– ident: e_1_3_3_29_2
  doi: 10.1677/jme.1.02058
– ident: e_1_3_3_36_2
  doi: 10.1073/pnas.122225699
– ident: e_1_3_3_8_2
  doi: 10.1242/dev.127.19.4277
– ident: e_1_3_3_28_2
  doi: 10.1210/endo.133.6.8243259
– ident: e_1_3_3_15_2
  doi: 10.1095/biolreprod56.2.293
– volume: 37
  start-page: 253
  year: 1989
  ident: e_1_3_3_27_2
  article-title: Response to the antiprogestagen RU 486 (mifepristone) during early pregnancy and the menstrual cycle in women
  publication-title: J Reprod Fertil Suppl
  contributor:
    fullname: Spitz IM
– ident: e_1_3_3_10_2
  doi: 10.1210/rp.57.1.339
– ident: e_1_3_3_33_2
  doi: 10.1177/0192623315570339
– ident: e_1_3_3_44_2
  doi: 10.1016/j.contraception.2012.08.002
– ident: e_1_3_3_35_2
  doi: 10.1016/j.cell.2015.04.052
– ident: e_1_3_3_17_2
  doi: 10.1210/en.2013-2150
– ident: e_1_3_3_37_2
  doi: 10.1210/en.2006-1561
– ident: e_1_3_3_5_2
  doi: 10.1016/j.yfrne.2011.01.001
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Snippet The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the...
Progesterone possesses an essential role in regulating female fertility, with prominent actions throughout the female reproductive axis. The neuroendocrine...
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SubjectTerms Animals
Biological Sciences
Exons
Female
Females
Fertility
Ligands
Luteinizing Hormone - antagonists & inhibitors
Mifepristone - pharmacology
Mutation
Progesterone - genetics
Progesterone - physiology
Rats
Reproduction - physiology
Sexual behavior
Transcription factors
Title Rethinking progesterone regulation of female reproductive cyclicity
URI https://www.jstor.org/stable/26469282
http://www.pnas.org/content/113/15/4212.abstract
https://www.ncbi.nlm.nih.gov/pubmed/27035990
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https://search.proquest.com/docview/1795863343
https://pubmed.ncbi.nlm.nih.gov/PMC4839436
Volume 113
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