Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients

Nekoonam, Saeid; Naji, Mohammad; Nashtaei, Maryam Shabani; Mortezaee, Keywan; Koruji, Morteza; Safdarian, Leili; Amidi, Fardin

doi:10.1007/s00404-017-4317-9

Cited by 29 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Which is in agreement with some reports in patients with PCOS or animal models of PCOS [16,17]. However, other studies reported that the PI3K/Akt signaling is overactivated in PCOS [32,33]. PCOS is a complex disease, and the PI3K/Akt signaling pathway is complicated and dependent on different cells and conditions, which may be the reason of the discrepancy results.…”

Section: Discussionsupporting

confidence: 91%

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

Gong

Luo

Fan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Growth hormone (GH) can reduce oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in GCs of patients with polycystic ovary syndrome (PCOS). Methods: Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-GH, n = 30) or without GH (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and ﬂuorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels were determined by enzyme-linked immunosorbent assay. Result(s): The present study found that compared with those in the non-PCOS and PCOS-GH groups, the ROS levels and apoptotic rates were significantly increased, whereas MMP was significantly decreased in the PCOS-C group GCs (P < 0.05). Compared with those in non-PCOS and PCOS-GH groups, mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly increased, whereas Bcl-2 was decreased in the GCs of the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were increased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were decreased in the GCs of the PCOS-C group, compared with those in the non-PCOS and PCOS-GH groups (P < 0.05). Conclusion: OS induced apoptosis and inactivated the PI3K/Akt signaling pathway in patients with PCOS. GH could improve apoptosis and activate the PI3K/Akt signaling pathway.Clinical Trial Registration Number: Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx). ChiCTR1800019437. Prospectively registered on October 20, 2018, http://www.chictr.org.cn/edit.aspx?pid=28663&htm= 4

show abstract

Section: Discussionsupporting

confidence: 91%

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

Gong

Luo

Fan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Follicular atresia is potentiated by androgens in the immature rat, and granulose cell apoptosis in rats is inducible by androgens [ 18 ]. Increased expression of AKT1 and AKT2 may be a possible mechanism linking HA to granulosa cell dysfunction in patients with HA PCOS [ 19 ]. Finally, testosterone may impact the endometrium.…”

Section: Discussionmentioning

confidence: 99%

Body mass index and basal androstenedione are independent risk factors for miscarriage in polycystic ovary syndrome

Yang

Lin

et al. 2018

Reprod Biol Endocrinol

View full text Add to dashboard Cite

BackgroundThere is limited literature investigating the effects of body mass index (BMI) and androgen level on in vitro fertilization (IVF) outcomes with a gonadotropin-releasing hormone (GnRH)-antagonist protocol in polycystic ovary syndrome (PCOS). Androgen-related variation in the effect of body mass index (BMI) on IVF outcomes remains unknown.MethodsIn this retrospective study, 583 infertile women with PCOS who underwent IVF using the conventional GnRH-antagonist protocol were included. Patients were divided into four groups according to BMI and androgen level: overweight- hyperandrogenism(HA) group, n = 96, overweight-non-HA group, n = 117, non-overweight-HA group, n = 152, and non-overweight-non-HA group, n = 218.ResultsA significantly higher number of oocytes were retrieved, and the total Gn consumption as well Gn consumption per day was significantly lower, in the non-overweight groups than in the overweight groups. The number of available embryos was significantly higher in the HA groups than in the non-HA groups. Clinical pregnancy rate was of no significant difference among four groups. Live-birth rates in the overweight groups were significantly lower than those in non-overweight-non-HA group (23.9, 28.4% vs. 42.5%, P<0.05). The miscarriage rate in overweight-HA group was significantly higher than that in non-overweight-non-HA group (45.2% vs. 14.5%, P<0.05). Multivariate logistic regression analysis revealed that BMI and basal androstenedione (AND) both acted as significantly influent factors on miscarriage rate. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis for BMI and basal AND on miscarriage rate were 0.607 (P = 0.029) and 0.657 (P = 0.001), respectively, and the cut-off values of BMI and basal AND were 25.335 kg/m2 and 10.95 nmol/L, respectively.ConclusionsIn IVF cycles with GnRH-antagonist protocol, economic benefits were seen in non-overweight patients with PCOS, with less Gn cost and more retrieved oocytes. BMI and basal AND were both significantly influential factors with moderate predictive ability on the miscarriage rate. The predictive value of basal AND on miscarriage was slightly stronger than BMI.

show abstract

“…Based on the network analysis, we obtained three proteins of interest—AKT1, IL6 and INSR. In the hyper-androgenic PCOS patients, high levels of AKT1 have been associated with GCs dysfunction [ 43 ]. In addition, IL6, IL1B1 and TNF are associated with increased susceptibility to PCOS [ 44 ], and INSR plays a role in compensatory hyperinsulinemia [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology approach to explore the mechanisms of Erxian decoction in polycystic ovary syndrome

Liu

Zhang

et al. 2018

Chin Med

View full text Add to dashboard Cite

BackgroundPolycystic ovary syndrome (PCOS) significantly affects women’s health and well-being. To explore the pharmacological basis of the Erxian decoction (EXD) action in PCOS therapy, a network interaction analysis was conducted at the molecular level.MethodsThe active elements of EXD were identified according to the oral bioavailability and drug-likeness filters from three databases: traditional Chinese medicine system pharmacology analysis platform, TCM@taiwan and TCMID, and their potential targets were also identified. Genes associated with PCOS and established protein–protein interaction networks were mined from the NCBI database. Finally, significant pathways and functions of these networks were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine the mechanism of action of EXD.ResultsSeventy active compounds were obtained from 981 ingredients present in the EXD decoction, corresponding to 247 targets. In addition, 262 genes were found to be closely related with PCOS, of which 50 overlapped with EXD and were thus considered therapeutically relevant. Pathway enrichment analysis identified PI3k-Akt, insulin resistance, Toll-like receptor, MAPK and AGE-RAGE from a total of 15 significant pathways in PCOS and its treatment.ConclusionsEXD can effectively improve the symptoms of PCOS and our systemic pharmacological analysis lays the experimental foundation for further clinical applications of EXD.

show abstract

Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients

Abstract: High expressions of AKT1 and AKT2 through possible relation with androgen may cause GCs dysfunction in the +HA PCOS patients.

Cited by 29 publications

References 37 publications

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

Body mass index and basal androstenedione are independent risk factors for miscarriage in polycystic ovary syndrome

A network pharmacology approach to explore the mechanisms of Erxian decoction in polycystic ovary syndrome

Contact Info

Product

Resources

About