SOCS (suppressor of cytokine signaling) proteins, also known as SSI (STAT-induced STAT inhibitor) proteins, have been shown to be negative regulators of cytokine receptor signaling via the Janus kinase signal transducer and activation of transcription (STAT; see OMIM 600555) pathway (the JAK/STAT pathway).
NCBI Summary:
This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]
General function
Comment
Cellular localization
Cytoplasmic
Comment
candidate123
Ovarian function
Luteolysis
Comment
Expression regulated by
Eicosanoids
Comment
Ovarian localization
Luteal cells
Comment
J. D. Curlewis, et al reported that a Prostaglandin F2 Analog Induces Suppressors of Cytokine Signaling-3 Expression in the Corpus Luteum of the Pregnant Rat.
PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and the authors have addressed the issue of whether luteolysis induced by prostaglandin F2 (PGF2 ) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF2 analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. They also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF2 may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.
Follicle stages
Corpus luteum
Comment
Maximal expression of Suppressors of Cytokine Signalling (SOCS) in the rat ovary occurs in late pregnancy. Anderson S et al. Maintenance of the rodent corpus luteum during pregnancy requires prolactin-receptor (PRL-R) signal transduction via STAT5. At the end of pregnancy prostaglandin F2alpha (PGF2alpha) induces luteal regression through many mechanisms, including down-regulation of PRL-R signaling. We have previously shown that a PGF2alpha analog upregulates Suppressors of Cytokine Signaling (SOCS) proteins in the corpus luteum of Day 19 pregnant rats leading to reduced STAT5 signaling. Here we examined endogenous SOCS expression and STAT5 signaling in the rat ovary during normal pregnancy and luteolysis. The mRNA expression of SOCS1, SOCS2 and SOCS3 and related Cytokine-inducible SH2-containing protein (CIS) was low in early pregnancy (Day 7), but significantly increased at mid-pregnancy (Days 10 and 13) associated with increased endogenous tyrosine phosphorylation (TyrP) of STAT5. In support of the notion that these changes are due to increasing placental lactogen levels at this time, we found that treatment with exogenous prolactin on Day 7 increased TyrP of STAT5 and induced SOCS mRNA expression, except SOCS3. After mid-pregnancy, further significant increases in SOCS3 and CIS mRNA expression were observed. Such changes in mRNA expression correlated with protein levels, with protein levels of both SOCS3 and CIS being maximal in late pregnancy (Days 19 to 21). In addition a significant reduction in TyrP of STAT5 was first observed on Day 20, with a further substantial decrease on Day 21. Therefore these results are consistent with the hypothesis that increased SOCS expression in the rat ovary during late pregnancy reduces STAT5 signaling which may be important in PGF2alpha-induced luteolysis.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome. Oz Gul O et al. (2017) Eighty-four subjects, premenopausal female patients (n = 42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n = 42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m(2), p < .001), HOMA-IR (3.1(1.8) vs.1.5 (1.0), p < .001), LDL-cholesterol (115.9(32.7) vs.100.7 (27.3)mg/dL, p = .03) and triglyceride (113.8(64.9) vs.83.3(36.3)mg/dL, p = .017) were significantly higher in patients. Groups were similar in terms of SOCS1-1478 CA/del polymorphism. No significant relation of this polymorphism was noted to PCOS and HOMA-IR. Our findings revealed no difference between groups in terms of the rate of SOCS1-1478 CA/del polymorphism, and no significant relation of this polymorphism to insulin resistance and PCOS status. Impact statement Polycystic ovary syndrome (PCOS), the most common cause of anovulation and the most commonly encountered form of female endocrine disease. SOCS proteins have been suggested to play a fundamental role in the negative feedback regulation of the JAK-STAT pathway, which is the major signalling pathway involved in a wide range of physiologic and pathologic processes, including inflammatory diseases, malignancies and immune disorders. Pathways involving the induction of suppression of SOCS proteins were also shown likely to be involved in mediating cytokine-induced insulin resistance. The present study was designed to determine the frequency of SOCS1-1478 CA/del gene polymorphism in patients with PCOS in relation to healthy controls and insulin resistance. Our findings revealed significantly higher rates of insulin resistance, obesity and dyslipidaemia in Turkish patients with PCOS compared with age-matched healthy controls, while no difference between study groups in terms of the rate of SOCS1-1478 CA/del polymorphism along with no significant relation of SOCS1-1478 CA/del polymorphism to insulin resistance and PCOS status. Future larger scale studies with the application of standardised diagnostic methods and criteria, and of state-of-the-art modern techniques including genomics, proteomics and pharmacogenetics would provide better understanding of the association between PCOS and genomic variants.//////////////////