MCID: PRG014
MIFTS: 42

Progesterone Resistance

Categories: Reproductive diseases

Aliases & Classifications for Progesterone Resistance

MalaCards integrated aliases for Progesterone Resistance:

Name: Progesterone Resistance 57 29 13 54 39 70
Pseudocorpus Luteum Insufficiency 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
progesterone resistance:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM® 57 264080
MedGen 41 C1849699
SNOMED-CT via HPO 68 258211005 6738008
UMLS 70 C1849699

Summaries for Progesterone Resistance

OMIM® : 57 Progesterone prepares the endometrium for blastocyst implantation and allows maintenance of pregnancy. The major sources of progesterone are the corpus luteum during the second half of the menstrual cycle and at the beginning of pregnancy, and the placenta. The main hormones responsible for stimulation of progesterone secretion are luteinizing hormone (LH) for the corpus luteum of the menstrual cycle and chorionic gonadotropin for the corpus luteum of pregnancy. Complete end-organ resistance to progesterone would be incompatible with reproductive competence in females. Males would not be expected to be affected since progesterone has no known function in men. Failure of the uterus to respond to progesterone would lead to the development of a 'constantly proliferative' endometrium incompatible with blastocyst implantation. Partial resistance to progesterone, on the other hand, would be expected to be associated with various degrees of incomplete maturation of the endometrium, perhaps expressed clinically as infertility or early abortions. The syndrome would present with the clinical and histologic picture of a luteal phase defect in which the life span of the corpus luteum and the plasma progesterone concentrations would be normal or elevated. (264080) (Updated 05-Apr-2021)

MalaCards based summary : Progesterone Resistance, also known as pseudocorpus luteum insufficiency, is related to endometriosis and endometrial hyperplasia. An important gene associated with Progesterone Resistance is PGR (Progesterone Receptor), and among its related pathways/superpathways are Gastric cancer and Glioma. The drugs Progesterone and Hormones have been mentioned in the context of this disorder. Affiliated tissues include uterus, placenta and ovary, and related phenotypes are female infertility and abnormality of metabolism/homeostasis

Related Diseases for Progesterone Resistance

Diseases related to Progesterone Resistance via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 121)
# Related Disease Score Top Affiliating Genes
1 endometriosis 30.4 PGR MIR29C ESR2 ESR1
2 endometrial hyperplasia 29.8 PGR KRAS ESR2 ESR1
3 endometrial disease 29.8 PGR ESR1 ERRFI1
4 ovarian disease 29.3 PGR MIR92A1 ESR2 ESR1
5 endometrial cancer 10.3
6 glassy cell carcinoma of the cervix 10.2 PGR ESR1
7 breast intraductal papillomatosis 10.2 PGR ESR1
8 intraductal papilloma 10.2 PGR ESR1
9 nipple carcinoma 10.2 PGR ESR1
10 bartholin's gland adenoma 10.2 PGR ESR1
11 bartholin's gland adenoid cystic carcinoma 10.2 PGR ESR1
12 uterine corpus adenosarcoma 10.2 PGR ESR1
13 adenosarcoma 10.2 PGR ESR1
14 bartholin's gland benign neoplasm 10.2 PGR ESR1
15 endosalpingiosis 10.2 PGR KRAS
16 chronic tympanitis 10.2 PGR ESR1
17 vestibular gland benign neoplasm 10.2 PGR ESR1
18 granulomatous endometritis 10.2 PGR ESR1
19 vulvar syringoma 10.2 PGR ESR1
20 lung leiomyoma 10.2 PGR ESR1
21 adult type testicular granulosa cell tumor 10.2 PGR ESR1
22 breast scirrhous carcinoma 10.2 PGR ESR1
23 oncocytic breast carcinoma 10.2 PGR ESR1
24 cervical clear cell adenocarcinoma 10.2 PGR ESR1
25 ovarian seromucinous carcinoma 10.2 PGR ESR1
26 breast papillary carcinoma 10.2 PGR ESR1
27 liver leiomyoma 10.2 PGR ESR1
28 intravenous leiomyomatosis 10.2 PGR ESR1
29 comedo carcinoma 10.2 PGR ESR1
30 breast adenoid cystic carcinoma 10.2 PGR ESR1
31 breast metaplastic carcinoma 10.2 PGR ESR1
32 intracranial meningioma 10.2 PGR ESR1
33 vulvar leiomyoma 10.2 PGR ESR1
34 nonmucinous bronchioloalveolar adenocarcinoma 10.2 ESR2 ESR1
35 bizarre leiomyoma 10.2 PGR ESR1
36 breast adenoma 10.2 PGR ESR1
37 lipid-rich carcinoma 10.2 PGR ESR1
38 breast malignant phyllodes tumor 10.2 PGR ESR1
39 prostate stromal sarcoma 10.2 PGR ESR1
40 progesterone-receptor negative breast cancer 10.2 PGR ESR1
41 intracystic papillary adenoma 10.2 PGR ESR1
42 bile duct cystadenoma 10.2 ESR2 ESR1
43 postmenopausal atrophic vaginitis 10.2 ESR2 ESR1
44 vaginitis 10.2 ESR2 ESR1
45 urethral benign neoplasm 10.2 PGR ESR1
46 apocrine sweat gland neoplasm 10.2 PGR ESR1
47 apocrine adenocarcinoma 10.1 PGR ESR1
48 cervical adenosarcoma 10.1 PGR ESR1
49 breast neuroendocrine neoplasm 10.1 PGR ESR1
50 biphasic synovial sarcoma 10.1 PGR ESR1

Graphical network of the top 20 diseases related to Progesterone Resistance:



Diseases related to Progesterone Resistance

Symptoms & Phenotypes for Progesterone Resistance

Human phenotypes related to Progesterone Resistance:

31
# Description HPO Frequency HPO Source Accession
1 female infertility 31 HP:0008222
2 abnormality of metabolism/homeostasis 31 HP:0001939

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
G U:
female infertility
normal menstrual cycle
normal luteal phase duration

Lab:
normal plasma immunoreactive lh and progesterone
histologically immature endometrium
decreased endometrial progesterone receptors

Clinical features from OMIM®:

264080 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Progesterone Resistance:

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.15 BCL6 DHCR24 ERRFI1 ESR1 ESR2 FKBP4
2 cardiovascular system MP:0005385 10.13 BCL6 ERRFI1 ESR1 ESR2 FKBP4 KRAS
3 integument MP:0010771 10.13 BCL6 DHCR24 ERRFI1 ESR1 ESR2 FKBP4
4 mortality/aging MP:0010768 10.1 BCL6 DHCR24 ERRFI1 ESR1 ESR2 FKBP4
5 digestive/alimentary MP:0005381 9.99 ERRFI1 ESR1 ESR2 FKBP4 KRAS SIRT1
6 limbs/digits/tail MP:0005371 9.93 ERRFI1 ESR1 ESR2 KRAS PGR SIRT1
7 liver/biliary system MP:0005370 9.91 BCL6 ERRFI1 ESR1 ESR2 KRAS SIRT1
8 no phenotypic analysis MP:0003012 9.87 BCL6 ERRFI1 ESR1 ESR2 KRAS PGR
9 neoplasm MP:0002006 9.85 ERRFI1 ESR1 ESR2 KRAS PGR SIRT1
10 normal MP:0002873 9.8 BCL6 ERRFI1 ESR1 ESR2 KRAS PGR
11 renal/urinary system MP:0005367 9.7 ERRFI1 ESR1 ESR2 FKBP4 HSD17B2 KRAS
12 reproductive system MP:0005389 9.61 BCL6 DHCR24 ERRFI1 ESR1 ESR2 FKBP4
13 respiratory system MP:0005388 9.1 BCL6 ERRFI1 ESR1 ESR2 KRAS SIRT1

Drugs & Therapeutics for Progesterone Resistance

Drugs for Progesterone Resistance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Progesterone Approved, Vet_approved Phase 2 57-83-0 5994
2 Hormones Phase 2
3 Progestins
4 Hormone Antagonists
5 Follicle Stimulating Hormone Early Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 SIRT1-1 Antagonist Therapy Before Embryo Transfer to Improve Endometrial Receptivity and Life Pregnancy Rates Not yet recruiting NCT04184323 Phase 2 EX-527 (Selisistat);Placebo
2 Variation of Progesterone in IVF Cycles Completed NCT03519776
3 Impact of Step-down Approach During Late Follicular Phase in Recombinant FSH-stimulation Dosage for IVF on Progesterone Level on the Day of Final Oocyte Maturation Completed NCT03356964 Early Phase 1 follicle stimulating hormone
4 Prospective Clinical Study of the Relationship Between Cancer Driving Mutations Found in Endometriotic Implants and the Development of Progesterone Resistance Recruiting NCT03756480

Search NIH Clinical Center for Progesterone Resistance

Genetic Tests for Progesterone Resistance

Genetic tests related to Progesterone Resistance:

# Genetic test Affiliating Genes
1 Progesterone Resistance 29 PGR

Anatomical Context for Progesterone Resistance

MalaCards organs/tissues related to Progesterone Resistance:

40
Uterus, Placenta, Ovary, Breast, Heart

Publications for Progesterone Resistance

Articles related to Progesterone Resistance:

(show top 50) (show all 138)
# Title Authors PMID Year
1
Pseudocorpus luteum insufficiency: a local defect of progesterone action on endometrial stroma. 57 61
217888 1979
2
Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. 54 61
20104427 2010
3
17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. 61 54
20108182 2010
4
The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of endometriosis. 61 54
19389829 2009
5
Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis. 61 54
19001520 2009
6
Progesterone resistance in endometriosis: link to failure to metabolize estradiol. 61 54
16406281 2006
7
Progesterone receptor isoform A but not B is expressed in endometriosis. 54 61
10946900 2000
8
ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis. 61
33706098 2021
9
CNR1 may reverse progesterone-resistance of endometrial cancer through the ERK pathway. 61
33640608 2021
10
Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. 61
33807739 2021
11
Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome. 61
33808965 2021
12
Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics. 61
33421806 2021
13
Nuclear factor-kappa B signaling in endometriotic stromal cells is not inhibited by progesterone owing to an aberrant endoplasmic reticulum stress response: a possible role for an altered inflammatory process in endometriosis. 61
33507306 2021
14
Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. 61
33640070 2021
15
Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer. 61
32805208 2021
16
The development of the human uterus: morphogenesis to menarche. 61
33395479 2021
17
Epigenetics of Estrogen and Progesterone Receptors in Endometriosis. 61
32700282 2020
18
Repurposing of antipsychotics perphenazine for the treatment of endometrial cancer. 61
32527541 2020
19
Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure. 61
32412587 2020
20
Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture. 61
32004675 2020
21
Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1†. 61
31494675 2020
22
miR-92a promotes progesterone resistance in endometriosis through PTEN/AKT pathway. 61
31863773 2020
23
Dienogest regulates apoptosis, proliferation, and invasiveness of endometriotic cyst stromal cells via endoplasmic reticulum stress induction. 61
31814016 2020
24
Diagnostic and therapeutic options in recurrent implantation failure. 61
32266059 2020
25
Expression of Membrane Progesterone Receptors in Eutopic and Ectopic Endometrium of Women with Endometriosis. 61
32733932 2020
26
An assessment of the multifactorial profile of steroid-metabolizing enzymes and steroid receptors in the eutopic endometrium during moderate to severe ovarian endometriosis. 61
31878927 2019
27
Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis. 61
30782101 2019
28
CRISPR/Cas9-Mediated Gene Knockout of ARID1A Promotes Primary Progesterone Resistance by Downregulating Progesterone Receptor B in Endometrial Cancer Cells. 61
31072420 2019
29
Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis? 61
31387263 2019
30
Endometriosis. 61
30994890 2019
31
Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis. 61
30270745 2019
32
Endometriosis and nuclear receptors. 61
30809650 2019
33
Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-κB signaling pathway. 61
30259980 2019
34
Rare genetic variants potentially involved in ovarian hyperstimulation syndrome. 61
30483911 2019
35
Differential expression of progesterone receptor isoforms related to PGR +331g/a polymorphism in endometriosis: A case-control study. 61
31435600 2019
36
Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B. 61
30443761 2019
37
Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line. 61
30813939 2019
38
Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis. 61
32063886 2019
39
Reviewing the role of progesterone therapy in endometriosis. 61
30044157 2019
40
Progesterone Resistance in Endometriosis: an Acquired Property? 61
29934050 2018
41
The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis. 61
30021652 2018
42
miR-194-3p Represses the Progesterone Receptor and Decidualization in Eutopic Endometrium From Women With Endometriosis. 61
29762665 2018
43
Human chorionic gonadotropin induces decidualization of ectopic human endometrium more effectively than forskolin in an in-vivo endometriosis model. 61
29886768 2018
44
Oestrogen, progesterone and stem cells: the discordant trio in endometriosis? 61
29514724 2018
45
The Wnt/β-catenin signaling in endometriosis, the expression of total and active forms of β-catenin, total and inactive forms of glycogen synthase kinase-3β, WNT7a and DICKKOPF-1. 61
29107840 2018
46
Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation. 61
29949806 2018
47
Weighted Gene Co-expression Network Analysis of Endometriosis and Identification of Functional Modules Associated With Its Main Hallmarks. 61
30369943 2018
48
[ENDOMETRIOSIS: A NEW APPROACH TO ETIOLOGY AND PATHOGENESIS (REVIEW)]. 61
29328022 2017
49
The impact of uterine immaturity on obstetrical syndromes during adolescence. 61
28578177 2017
50
Aldo-keto reductase activity after diethylhexyl phthalate exposure in eutopic and ectopic endometrial cells. 61
28651148 2017

Variations for Progesterone Resistance

Expression for Progesterone Resistance

Search GEO for disease gene expression data for Progesterone Resistance.

Pathways for Progesterone Resistance

Pathways related to Progesterone Resistance according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.46 PGR KRAS ESR2 ESR1
2
Show member pathways
12.34 KRAS ESR2 ESR1 ERRFI1
3
Show member pathways
12.15 PGR KRAS FKBP4 ESR2 ESR1
4 11.85 SIRT1 MIR92A2 MIR92A1 MIR29C KRAS
5 11.84 SIRT1 KRAS ESR1
6
Show member pathways
11.77 SIRT1 KRAS BCL6
7
Show member pathways
11.61 PGR KRAS ESR1
8 11.53 KRAS ESR2 ESR1
9
Show member pathways
11.45 PGR ESR2 ESR1
10 10.97 ESR2 ESR1
11 10.93 ESR2 ESR1
12 10.16 KRAS ESR2 ESR1
13 9.86 ESR2 ESR1

GO Terms for Progesterone Resistance

Cellular components related to Progesterone Resistance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular vesicle GO:1903561 9.13 MIR92A2 MIR92A1 MIR29C
2 mitochondrion GO:0005739 9.1 SIRT1 PGR MIR29C KRAS FKBP4 ESR2

Biological processes related to Progesterone Resistance according to GeneCards Suite gene sharing:

(show all 32)
# Name GO ID Score Top Affiliating Genes
1 transcription initiation from RNA polymerase II promoter GO:0006367 9.82 PGR ESR2 ESR1
2 negative regulation of angiogenesis GO:0016525 9.77 MIR92A2 MIR92A1 MIR29C
3 negative regulation of cell growth GO:0030308 9.76 SIRT1 ESR2 BCL6
4 positive regulation of apoptotic process GO:0043065 9.72 SIRT1 MIR92A2 MIR92A1 MIR29C BCL6
5 miRNA mediated inhibition of translation GO:0035278 9.69 MIR92A2 MIR92A1 MIR29C
6 positive regulation of sprouting angiogenesis GO:1903672 9.65 MIR92A2 MIR92A1
7 negative regulation of JNK cascade GO:0046329 9.65 MIR92A2 MIR92A1
8 cellular response to fatty acid GO:0071398 9.65 MIR92A2 MIR92A1
9 negative regulation of cellular senescence GO:2000773 9.64 SIRT1 BCL6
10 regulation of blood vessel diameter GO:0097746 9.63 MIR92A2 MIR92A1
11 steroid hormone mediated signaling pathway GO:0043401 9.63 PGR ESR1
12 cellular response to low-density lipoprotein particle stimulus GO:0071404 9.62 MIR92A2 MIR92A1
13 negative regulation of nitric oxide biosynthetic process GO:0045019 9.62 MIR92A2 MIR92A1
14 negative regulation of cell-matrix adhesion GO:0001953 9.61 MIR29C BCL6
15 positive regulation of cellular senescence GO:2000774 9.61 SIRT1 KRAS
16 intracellular estrogen receptor signaling pathway GO:0030520 9.6 ESR2 ESR1
17 negative regulation of JUN kinase activity GO:0043508 9.58 MIR92A2 MIR92A1
18 positive regulation of leukocyte adhesion to vascular endothelial cell GO:1904996 9.57 MIR92A2 MIR92A1
19 negative regulation of hydrogen peroxide-induced cell death GO:1903206 9.56 MIR92A2 MIR92A1
20 positive regulation of monocyte chemotactic protein-1 production GO:0071639 9.55 MIR92A2 MIR92A1
21 positive regulation of acute inflammatory response GO:0002675 9.54 MIR92A2 MIR92A1
22 positive regulation of necrotic cell death GO:0010940 9.52 MIR92A2 MIR92A1
23 positive regulation of metalloendopeptidase activity GO:1904685 9.49 MIR92A2 MIR92A1
24 negative regulation of smooth muscle cell apoptotic process GO:0034392 9.48 MIR92A2 MIR92A1
25 ovulation from ovarian follicle GO:0001542 9.46 SIRT1 PGR
26 positive regulation of leukocyte adhesion to arterial endothelial cell GO:1904999 9.43 MIR92A2 MIR92A1
27 negative regulation of endothelial cell-matrix adhesion via fibronectin GO:1904905 9.4 MIR92A2 MIR92A1
28 vascular endothelial cell response to fluid shear stress GO:0097699 9.37 MIR92A2 MIR92A1
29 negative regulation of collagen biosynthetic process GO:0032966 9.33 MIR92A2 MIR92A1 ERRFI1
30 positive regulation of endothelial cell activation GO:1904989 9.26 MIR92A2 MIR92A1
31 intracellular steroid hormone receptor signaling pathway GO:0030518 9.13 PGR ESR2 ESR1
32 negative regulation of gene expression GO:0010629 9.1 SIRT1 PGR MIR92A2 MIR92A1 MIR29C ESR1

Molecular functions related to Progesterone Resistance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.91 SIRT1 PGR KRAS ESR2 ESR1 BCL6
2 sequence-specific DNA binding GO:0043565 9.71 PGR ESR2 ESR1 BCL6
3 enzyme binding GO:0019899 9.55 SIRT1 PGR ESR2 ESR1 DHCR24
4 nuclear receptor activity GO:0004879 9.5 PGR ESR2 ESR1
5 estrogen receptor activity GO:0030284 9.37 ESR2 ESR1
6 estrogen response element binding GO:0034056 9.26 ESR2 ESR1
7 steroid binding GO:0005496 9.13 PGR ESR2 ESR1
8 steroid hormone receptor activity GO:0003707 8.8 PGR ESR2 ESR1

Sources for Progesterone Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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