Serum Concentrations Of Activin Research Articles

Activin A concentrations in human cerebrospinal fluid are age-dependent and elevated in meningitis

Objective Activin A, and its binding protein, follistatin (FS), are expressed in the central nervous system (CNS). We have previously shown elevated concentrations of FS in the cerebrospinal fluid (CSF) of patients with meningitis and increased concentrations of activin A in the CSF of rabbits with bacterial meningitis. Methods We measured CSF and serum concentrations of activin A and FS in normal subjects and in patients with various neurological diseases using previously validated immunoassays specific for activin A or FS. Results In healthy persons, serum concentrations of both activin A and FS were age-dependent. In CSF, concentrations of activin A ranged from 0.03 to 0.33 ng/ml and were strongly correlated with age in both sexes, whereas FS CSF concentrations were below the assay detection limit in most of the patients. Activin A concentrations in CSF of patients with various neurological diseases, including meningitis, chronic inflammatory CNS diseases, neurodegenerative diseases, tumors in the CNS, cerebral ischemia, intracerebral/subarachnoid hemorrhages, subdural hemorrhages and epileptic seizures, were compared with age- and sex-matched control patients. The comparisons revealed significantly elevated concentrations of activin A in patients with meningitis ( P = 0.017). Serum concentrations of activin A or FS were not affected by any of the neurological diseases examined. Conclusions Our results show for the first time that in normal subjects concentrations of activin A in CSF are correlated with age, and furthermore, that activin A CSF concentrations are elevated in patients with meningitis. The latter underlines a role for activin A in acute inflammatory processes within the CNS.

Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre‐eclampsia in type I diabetic pregnancies

Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful as predictors of pre-eclampsia. In a prospective study, maternal serum was analyzed for activin A and inhibin A in 115 women with type 1 diabetes at 10, 14, 22, 28, and 33 weeks of gestation. Fourteen women (12%) developed pre-eclampsia (26-37 weeks of gestation) and 101 did not. The two groups were comparable regarding age, body mass index, and diabetes duration. There was no difference between serum concentrations of activin A and inhibin A in women developing pre-eclampsia and women who did not at any gestational period. Serum concentrations of activin A and inhibin A could not predict preeclampsia in type I diabetes.

Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia.

Activin is a growth and differentiation factor of many cell types, and has recently been implicated in inflammatory processes. Clinical data linking activin and its binding protein, follistatin (FS), are lacking. We measured serum levels of activin and FS in patients diagnosed with septicemia. Eight male and seven female patients of different ages, various forms of septicemia and different clinical outcome were investigated and compared with age- and sex-matched healthy controls. Serum concentrations of FS, activin, C-reactive protein (CRP) and blood leukocyte counts were determined during septicemia. The median of the maximum activin concentrations of septicemic patients was 3.9-fold higher than in age- and sex-matched healthy control subjects (P<0.01); the median of the maximum FS concentrations was 2.6-fold higher (P<0.01). The highest increase of activin in septicemic patients was approximately 15.8-fold, whereas FS increased by up to 13.2-fold above normal. FS, activin and CRP serum levels generally paralleled each other, but were not correlated with leukocyte counts or clinical outcome. Circulatory concentrations of activin and FS are elevated in patients diagnosed with septicemia, consistent with potential roles in the systemic inflammatory response.

Serum activin A, inhibin A, and follistatin concentrations in preeclampsia or small for gestational age pregnancies

OBJECTIVE: To determine whether maternal serum activin A, inhibin A, and follistatin concentrations in idiopathic small for gestational age (SGA) pregnancies are similar to those in normal pregnancies or elevated as in preeclampsia.METHODS: Maternal serum activin A, inhibin A, and follistatin concentrations were determined in 1) nulliparous women with idiopathic SGA (birth weight <10th percentile; n = 18), preeclampsia (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg plus proteinuria ≥2+ or >0.3 g/24h; n = 22), and normotensive controls, matched for gestational age at sampling (n = 22), and 2) a longitudinal series of samples collected at five intervals throughout pregnancy from nulliparous women with idiopathic SGA (n = 19), preeclampsia (n = 22), preeclampsia plus SGA (n = 15), or who had uncomplicated pregnancies (n = 20).RESULTS: Serum concentrations of activin A and inhibin A were similar in idiopathic SGA pregnancies to controls. In preeclampsia, activin A and inhibin A levels were markedly increased compared with controls or women with idiopathic SGA (P < .001), particularly in those with early-onset disease. Follistatin concentrations were only modestly (<twofold) elevated in preeclampsia (P < .001). In the longitudinal study, serum activin A or inhibin A concentrations were increased in women who later developed preeclampsia, whereas in women with idiopathic SGA pregnancy, a small overall increase in activin A levels was observed.CONCLUSIONS: In contrast to women with preeclampsia, normotensive women with SGA pregnancies do not have markedly elevated circulating levels of activin A and inhibin A. These data support the hypothesis that increased serum activin A concentrations in preeclampsia may be a manifestation of maternal disease rather than just a marker of abnormal placentation.

Serum activin A and inhibin A elevated in pre-eclampsia: no relation to insulin sensitivity.

To assess the possible role of serum levels of activin A, inhibin A and pro-alpha inhibin (pro-alphaC) in insulin sensitivity in pre-eclampsia. A prospective study. Helsinki University Central Hospital. Twenty-two nulliparous women with proteinuric pre-eclampsia and 16 healthy nulliparous controls in the third trimester of pregnancy. Serum samples were collected before and after intravenous injection of glucose (0.3 g/kg) and insulin (0.03 IU/kg) (the minimal model for testing insulin sensitivity), and were assayed for activin A, inhibin A and pro-alphaC. Comparison of the levels of activin A, inhibin A and pro-alphaC between pre-eclamptic and healthy pregnant women, and the association of these proteins with insulin sensitivity. In pre-eclampsia elevated levels of activin A (139%, P = 0.0001), inhibin A (39%, P = 0.003), and pro-alphaC (92%, P = 0.0008) were observed. The amount of proteinuria (0.3-10.5 g/day) correlated positively with serum concentrations of activin A (P = 0.01) and inhibin A (P = 0.02). These glycoproteins were not associated with insulin sensitivity either in women with pre-eclampsia or controls. A 2.9-fold rise in blood glucose and a 52.5-fold rise in insulin during testing using the minimal model were not accompanied by any significant changes in activin A, inhibin A, and pro-alphaC. Activin A, inhibin A, and pro-alphaC are elevated in pre-eclampsia but do not appear to relate to the insulin sensitivity in pre-eclamptic or normal pregnancies.

Measurement of activin in biological fluids by radioimmunoassay, utilizing dissociating agents to remove the interference of follistatin.

Activin, a dimer of the beta-subunits of inhibin, is a member of the transforming growth factor beta (TGF-beta) superfamily of growth factors and has a widespread range of actions in a variety of tissues. The investigation of the physiology of activin action has been facilitated in recent years by the availability of immunoassays in addition to bioassays. Follistatin has been shown to bind to activin with a high affinity and therefore interferes in both radioimmunoassays and enzyme-linked immunosorbent assays (ELISAs). In this study we examined the effect of various surfactants and 1.4-dioxane on the measurement of activin in the presence of follistatin by radioimmunoassay. The addition of a combination of sodium deoxycholate. Tween 20 and sodium dodecyl sulphate removed the interference of follistatin in the radioimmunoassay. The measured content of activin in male rat serum, human male serum, human female serum and bovine follicular fluid rose from 3.29 to 4.15, < 0.48 to 2.87, 2.42 to 4.17 and 30.9 to 85.6 ng/ml, respectively, when assayed in the presence of the dissociating reagents. It was unclear whether the altered potencies were due to a dissociation of the follistatin/activin complex rather than the exposure of the epitope on activin recognized by the antiserum. Serum concentrations of activin were lower than those found in testicular cytosols, and after castration no change in serum activin levels was observed, suggesting that the testis does not contribute significantly to circulating activin levels. The use of the dissociating reagents in the radioimmunoassay will enable studies to be carried out that more accurately measure the activin content of various biological fluids, and thus lead to a greater understanding of the physiology of this growth factor.