NCBI Summary:
The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Serum soluble glycoprotein 130 concentration is inversely related to insulin sensitivity in women with polycystic ovary syndrome. Nikolajuk A et al. (2010) Insulin resistance might play a role in the pathogenesis of polycystic ovarian syndrome (PCOS). The family of glycoprotein 130 (gp130) cytokines could influence insulin action. One of these cytokines is interleukin (IL)-6, which exerts a short-term insulin-sensitizing effect, whereas in a long-term period, it might induce insulin resistance. Some other gp130 activators are supposed to have beneficial metabolic effects. Gp130 is present in the circulation in the soluble form (sgp130), which inhibits intracellular gp130 signaling. The aim of the present study was to estimate the relation between sgp130 and insulin sensitivity in women with PCOS. We studied 78 women with PCOS (35 lean and 43 obese) and 34 healthy women (18 lean and 16 obese). The euglycemic-hyperinsulinemic clamp and the measurements of serum sgp130, IL-6, soluble IL-6 receptor (sIL-6R), and sex hormones were performed. Both obesity and PCOS were characterized by an increased sgp130 (P < 0.0001 and P = 0.0002, respectively). sIL-6R concentration was lower (P = 0.0036) in women with PCOS independently of obesity. Serum sgp130 was negatively correlated with insulin sensitivity when control and PCOS women were analyzed together (r = -0.36, P < 0.0001) and in the PCOS subjects separately (r = -0.34, P = 0.002). In multiple regression analysis, this correlation was significant after adjustment for BMI, waist, percent of body fat, postload glucose and insulin, triglycerides, and high-sensitive C-reactive protein. Serum sgp130 is inversely and independently associated with insulin sensitivity in women with PCOS. An increased serum sgp130 in obesity and PCOS suggests an inhibition of intracellular gp130 signaling in insulin-resistant conditions.//////////////////
Ovarian function
Ovulation, Steroid metabolism
Comment
Leukemia Inhibitory Factor is Necessary for Ovulation in Female Rhesus Macaques. Murphy MJ et al. (2016) Although the requirement of pituitary-derived luteinizing hormone (LH) for ovulation is well documented, the intrafollicular paracrine and autocrine processes elicited by LH necessary for follicle rupture are not fully understood. Evaluating a published rhesus macaque periovulatory transcriptome database revealed that mRNA encoding leukemia inhibitory factor (LIF) and its downstream signaling effectors are upregulated in the follicle after animals receive an ovulatory stimulus (human chorionic gonadotropin; hCG). Follicular LIF mRNA and protein levels are below the limit of detection prior to the administration of hCG, but increase significantly 12 h thereafter. Downstream LIF receptor signaling components including interleukin-6 signal transducer (IL6ST), the receptor associated janus kinase (JAK) 1 and the transcription factor signal transducer and activator of transcription (STAT) 3 also exhibit increased expression in the rhesus macaque follicle 12 h after administration of an ovulatory hCG bolus. A laparoscopic ovarian evaluation 72 h after the injection of a LIF antagonist (soluble LIF receptor; sLIFR) into the rhesus macaque preovulatory follicle and hCG administration revealed blocking LIF action prevented ovulation (typically occurs 36 to 44 h post-hCG). Moreover, ovaries removed 52 h after both hCG and intrafollicular sLIFR administration confirmed ovulation was blocked as evidenced by the presence of an intact follicle and a trapped cumulus-oocyte complex. These findings give new insight into the role of LIF in the primate ovary and could lead to the development of new approaches for the control of fertility.//////////////////
Expression regulated by
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Age-associated changes in granulosa cell transcript abundance in equine preovulatory follicles. Sessions-Bresnahan DR et al. (2015) Age-related changes in follicle paracrine signalling are not defined, and follicular gene transcript abundance could predict oocyte viability. Granulosa cells from preovulatory follicles of mares considered Young (n=12; 4-14 years), Mid-aged (n=9; 15-19 years) and Old (n=14; 20-27 years) were evaluated for transcript abundance related to systemic and follicle-specific pathways. Gene transcript abundance for receptors of insulin, adiponectin and peroxisome proliferating factor-? were higher or tended to be higher in Mid-aged or Old than Young mares. Transcript abundance for interleukin (IL)-6 was elevated in Old versus Young mares, and IL-6 signal transducer was elevated in Old versus younger groups. Expression of tumour necrosis factor (TNF) receptor superfamily member 1A was higher in Mid-aged than Young mares, whereas TNF-inducible gene 6 protein mRNA tended to decrease in Mid-aged versus Young and Old mares. Genes for LH receptor and steroidogenic acute regulatory protein tended to be increased in Old versus Mid-aged and Young mares, respectively. Young and Old mares had higher mRNA for tissue-type plasminogen activator than Mid-aged mares. Thioredoxin-2 mRNA was higher in Old than younger groups. We observed age-related changes in mRNA of receptors for metabolic hormones, inflammatory processes, steroidogenic hormones, tissue remodelling and mitochondrial function, which could contribute to and/or mark alterations in follicular function and fertility.//////////////////
Salmassi A, et al 2001 reported the interaction of interleukin-6 on human granulosa cell steroid
secretion.
Iimmunocytochemical methods indicated the
localization of the extracellular domain of the IL-6-receptor and its
associated signal transducer glycoprotein gp 130 on the surface of granulosa
cells (GCs). The possibility that IL-6 may also influence the basal and
FSH-stimulated production of estradiol (E2) and progesterone (Prog) by GCs in
vitro was also investigated.
GCs were obtained from infertile patients undergoing in vitro fertilization
and embryo transfer treatment and cultured for 72 h or were given increasing
concentrations of human recombinant IL-6 (8-128 pg/ml) in the absence or
presence of FSH (96 U/ml). For the time-course studies, FSH-stimulated GCs
were treated in the absence or presence of IL-6 (128 pg/ml) and supernatants
were assayed at 24 h intervals (24-96 h) for E2 and Prog productions. The
results show that increasing amounts of IL-6 significantly inhibit E2
production in the absence or presence of FSH vs untreated controls (P=0.025 at
IL-6 = 128 pg/ml and P=0.016 at IL-6 = 16 pg/ml respectively). IL-6 also
inhibited FSH-stimulated but not unstimulated Prog release (P = 0.038 at IL-6
= 8 pg/ml).
Follicle stages
Preovulatory, Corpus luteum
Comment
Telleria CM et al studied the expression of interleukin-6 in the pregnant rat corpus luteum and its
regulation by progesterone and glucocorticoid.
Using semiquantitative RT-PCR, mRNA encoding both components of the IL-6 receptor [the ligand-binding subunit (IL-6 R) and the IL-6 R-associated signal transducer (gp130)] were found to be highly expressed in corpora lutea throughout pregnancy.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Using Cre-loxP-mediated recombination to generate mice harboring a ventricular-restricted knockout of the gp130 cytokine
receptor, Hirota et al. (1999) demonstrated a critical role for a gp130-dependent myocyte survival pathway in the transition
to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure
overload, these mice displayed rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis compared
with the control mice, which exhibited compensatory hypertrophy.
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: GP130, the shared receptor for the LIF/IL6 cytokine family in the mouse, is not required for early germ cell differentiation, but is required cell-autonomously in oocytes for ovulation Molyneaux KA,.
GP130 is the shared receptor for members of the IL6 family of cytokines. Members of this family have been shown to enhance the survival of migratory (E10.5) or postmigratory (E12.5) murine primordial germ cells (PGCs) in culture; however, it is uncertain what role these cytokines play during PGC development in vivo. We have examined PGC numbers in E13.5 GP130-deficient mouse embryos and found that males exhibited a slight decrease in PGC numbers; females were normal. Also, we used the Cre-loxP system to inactive GP130 specifically in germ cells and found that this resulted in a fertility defect in females. These animals were found to have a slight reduction in the number of primary follicles and a major defect in ovulation. This data suggests that GP130 is required in female germ cells for their normal function, but is dispensable in male germ cells.