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[Modifications in alpha 2 globulins, gamma globulins and in rheumatoid factor during gold salt therapy in rheumatoid arthritis].

A total dose of g 1.071, given as hydrosoluble salts for a 12 month period, showed a significant decrease in serum gamma globulins along with clinical improvement in 17 patients affected with rheumatoid arthritis. A decrease in alpha 2 globulins and in rheumatoid factor titre was observed too, but it was not significant. The data suggest that in rheumatoid arthritis the gold therapy might also be effective on the immunological disease mechanism.

Adult↗

[Seed globulins from legumes. III. Seed globulins from broad bean (Vicia faba L.)].

The seed globulins from Vicia faba predominantly consist of two components, vicilin and legumin, which are exclusively deposited within the protein bodies of the storage cotyledons. The globulin biosynthesis commences with high intensity within a distinct phase during seed development as a consequence of reactivated genetic information. Isolation and purification of vicilin and legumin were achieved by a combination of zone precipitation, ion exchange chromatography, and gel filtration. Purity was controlled by disc electrophoresis on polyacrylamide e gels at pH 4.3 and by two dimensional immunoelectrophoresis, respectively. Vicilin prepared by zone precipitation and ion exchange chromatography consists of several serologically different proteins. One of them occupies the legumin position on polyacrylamide gels, although not identic with legumin, as revealed by tandem immunoelectrophoresis. The serological nonrelationship of vicilin and legumin was confirmed. Vicilin is characterized by micro heterogeneity which seems to indicate a molecular polymorphism.

Globulins↗

A study on gelation of soybean globulin solutions. Part 4. Effect of gelation conditions on the visco-elastic properties and structure of thermotropic gels of soybean globulin fraction.

To the study of the structure and properties of the thermotropic soybean globulin fraction (SGF) gels the stress relaxation and electron microscopy techniques has been applied. The value of slope of normalized relaxation function was used as a characteristic of relaxation properties of SGF gels. This value characterizes the velocity of the gels relaxation processes. It has been found that this characteristic is determined only by the gels' heating temperatures. Using the differential scanning microcalorimetric technique it was shown that the changes of the slope of normalized relaxation function of SGF gels are controlled only by heating temperature. The reason for this lies in the changes of the composition of the denaturation product of SGF gels. The increase is shown of the shear moduli of gels prepared at other than optimum temperatures by additional heating under optimal gelation conditions. That is a result of existence of a sol-fraction. The most significant increase of shear moduli is found for the SGF gels, sol-fraction of which is native 11S globulin. A correlation has been established between the changes of SGF gels' structure obtained from the dates of rheological measurements and electron microscopy technique.

Calorimetry, Differential Scanning↗

Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men.

The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.

Adult↗

Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone.

The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), total and absolute free testosterone were investigated in groups of 10 healthy volunteers. All preparations contained about the same amount of ethinylestradiol but they differed in type and/or dose of progestagen. The progestagens studied were: levonorgestrel (LNG; in mono- and triphasic preparations), norethisterone (NET; in monophasic preparation), desogestrel (DSG; in mono- and biphasic preparations) and gestodene (GSD; in triphasic preparation), all 19-nortestosterone derivatives, and the anti-androgen cyproterone acetate (CPA) in a monophasic preparation. Differences observed in SHBG level, which reflect the estrogen-androgen balance, can be attributed to the intrinsic androgenic (or anti-androgenic) properties of the progestagens, and were in agreement with the results of published receptor binding studies, performed in vitro. Based on our results the following ranking (high to low) can be made with respect to the androgenicity of the preparations: monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA. An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG, a marker for estrogenic activity. All preparations containing a 19-nortestosterone derived progestagen, independent of their type and dose, induce a similar rise in CBG, whereas the preparation with cyproterone acetate induced an even higher CBG level. Irrespective of the effect on total testosterone, which varies between the preparations, the absolute free testosterone level decreased to a comparable degree for all preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Changes in serum sex hormone-binding globulin and in serum non-sex hormone-binding globulin-bound testosterone during prepuberty in boys.

Much evidence suggests that sex hormone-binding globulin (SHBG) influences the delivery of sex steroids to cells, probably by playing an important role in the distribution of serum sex hormones between SHBG-bound, albumin (HSA)-bound and free fractions. Recent evidence also suggests that HSA-bound testosterone (T), the major constituent of non-sex hormone-binding globulin-bound T, is biologically important. To examine the potential exposure of peripheral tissues to T during prepubertal years, the serum concentration of SHBG as well as the distribution of serum T in SHBG-bound, HSA-bound, free and non-SHBG-bound fractions was studied in 80 normal boys aged 0.5-14 yr, all at Tanner's stage G1 of sexual development. A gradual decrease in serum SHBG as a function of age was found without significant changes in the Ka of SHBG-dihydrotestosterone association. While regression analysis of serum total T vs age showed a 2.6-fold increase from 0.5 to 14 yr of age, those of non-SHBG-found, HSA-bound and free T vs age showed 8- to 9-fold increases during the same period. On the other hand, SHBG-bound T had only a 1.9-fold increase. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6 to 30.4%, the relative increment being greater for HSA-bound T than for free T. It is concluded that, with advancing age, there is a progressive increase in the T exposure of all tissues in normal prepubertal boys. It is speculated that, at the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.

Adolescent↗

Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors.

The cDNA nucleotide sequences and the deduced amino acid sequences of human corticosteroid binding globulin (hCBG), human testosterone-estradiol binding globulin (hTeBG), and rat androgen binding protein (rABP) were determined. Studies of the steroid binding sites suggest they are toward the carboxy-terminus in hTeBG and rABP and more central in hCBG. hCBG has remarkable sequence homology with members of a superfamily whose functions have diverged; these include thyroxine-binding protein, serine protease inhibitors, egg white proteins, and angiotensinogen. hTeBG and rABP have a 68% amino acid sequence identity. Hybridization studies suggest that hTeBG is probably even more closely related, if not identical, to hABP. The carboxy-terminal sequences of hTeBG and rABP are also similar to that of protein S, a vitamin-K-dependent clotting factor. There were no nucleotide or amino acid sequence homologies between hCBG, hTeBG, or rABP and other steroid binding proteins such as steroid receptors, albumin, alpha-fetoprotein, and vitamin D binding protein. We conclude that the "extracellular steroid binding proteins" and steroid receptors do not appear to have descended from a common ancestor.

Amino Acid Sequence↗

Effects of desogestrel, levonorgestrel and lynestrenol on serum sex hormone binding globulin, cortisol binding globulin, ceruloplasmin and HDL-cholesterol.

The effects of 0.125 mg daily doses of the new progestagen, desogestrel, 0.125 mg of levonorgestrel or 5 mg of lynestrenol on serum sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), ceruloplasmin and HDL-cholesterol were studied in 30 healthy female volunteers to compare the possible androgenic and oestrogenic effects of these contraceptive steroids in vivo. All the progestagens in the applied dosages decreased SHBG and HDL-cholesterol concentrations, suggesting some androgenicity. Lynestrenol increased ceruloplasmin and CBG concentrations, indicating weak oestrogenic effects of the steroid. During desogestrel treatments, CBG and ceruloplasmin concentrations remained unchanged. After 30 days treatment with levonorgestrel there was a slight decrease (P less than 0.05) in ceruloplasmin concentrations. Thirty days after finishing the progestagen treatments serum protein concentrations were normal. In conclusion, at the doses used and under the present test conditions the progestagens studied had a weak androgen-like effect and lynestrenol also showed weak oestrogenic activity, as determined by their effects on serum proteins.

Adolescent↗

Sex hormone-binding globulin and thyroxine-binding globulin levels in premature thelarche.

Premature thelarche is defined as the isolated development of breast tissue in girls less than 8 years of age. Although breast development is an estrogen-dependent process, these girls do not have elevated serum estrogen levels, and the hormonal basis for their condition is unclear. We studied the levels of two estrogen-dependent transport proteins, sex hormone-binding globulin (SHBG) and thyroxine-binding globulin (TBG), in order to determine if there was evidence for a more subtle estrogen effect in girls with premature thelarche. SHBG levels in girls with premature thelarche were not significantly different from those of prepubertal girls of the same ages and were significantly lower than those in girls undergoing pubertal development at the appropriate age (P less than 0.05) and in normal women (P less than 0.001). There was no statistically significant difference in TBG levels between the girls with premature thelarche and prepubertal controls. There was also no significant difference in TBG levels between prepubertal girls and girls in early puberty. In contrast, women had TBG levels that were significantly lower than those in all girls studied. We conclude that the estrogen exposure (whether endogenous or exogenous) of girls with premature thelarche is less than that of girls in early true puberty and similar to that of other prepubertal girls. Further, changes in serum TBG are not as sensitive an indicator of estrogen effect as is breast development or changes in SHBG. This study also suggests that large amounts of exogenous estrogens are not an element in the development of premature thelarche.

Adolescent↗

Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin.

Two human serum proteins, corticosteroid-binding globulin (CBG) and sex-hormone-binding globulin (SHBG), were purified to homogeneity by the application of a combination of three different modes of chromatography. Human pregnancy serum was fractionated with ammonium sulphate. SHBG (50% pellet) and CBG (80% pellet) were then purified by affinity chromatography on tresyl-activated Sepharose with 15-aminopentadecanoic acid (for SHBG) and 1,12-diaminododecane (for CBG) as spacers and 17 zeta-aminoethyl-5 alpha-androstan-3 beta,17-diol (for SHBG) and 17 alpha-hydroxy-4-androsten-3-one-17 beta-carboxylic acid (for CBG) as specific ligands for these two proteins. The eluate was injected into a Mono Q anion-exchange column. Fractions containing SHBG or CBG were finally purified by liquid-liquid chromatography on Lipar-Gel 750. This chromatographic sequence clearly separated SHBG and CBG from other proteins, mainly serum albumin, without a loss of protein or binding activity.

Chromatography, Affinity↗

Treatment of childhood acute immune thrombocytopenic purpura with anti-D immune globulin or pooled immune globulin.

OBJECTIVE: To evaluate the effectiveness of initial treatment of children with acute immune thrombocytopenic purpura (ITP) with anti-D immune globulin (anti-D) or pooled IgG immune globulin (IVIg). STUDY DESIGN: The medical charts of 33 children diagnosed with acute ITP from May 1995 to October 1997 were reviewed. Patient data were eligible for analysis if, for the new diagnosis of acute ITP, the patient had received either anti-D at 45 to 50 microg/kg (WinRho SD, NABI) or IVIg at 0.8 to 1 g/kg (Gammagard SD, Baxter-Highland). The platelet response time for each treatment group was compared by the Mann-Whitney U test. RESULTS: Time to achieve a platelet count >/=20 x 10(9 )/L (20,000/mm3 ) was 1.54 +/- 0.51 days in the IVIg group (n = 13) and 1.26 +/- 0.82 days in the anti-D group (n = 14) (P =.34). Time to achieve a platelet count >/=40 x 10(9 )/L (40,000/mm3 ) was 1.77 +/- 0.74 and 1.49 +/- 1.01 days for the IVIg and anti-D groups, respectively (P =.32). Children given IVIg were hospitalized for 2.1 +/- 0.87 days, whereas those given anti-D were hospitalized for 1.94 +/- 1.08 days. A net decrease in hemoglobin concentration was observed after receipt of IVIg (9.1 +/- 7.3 g/L [0.91 +/- 0.73 g/dL]) and after anti-D therapy (4.5 +/- 10.3 g/L [0.45 +/- 1.03 g/dL], P =.23). No patient required intervention for hemolysis. CONCLUSIONS: In this retrospective analysis anti-D was as effective as IVIg for the treatment of acute ITP in children. However, randomized, controlled trials are needed to establish the role of anti-D in the treatment of acute ITP in children.

Adolescent↗

Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis.

Recently, much evidence has indicated that sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) play a role in the intracellular action of sex steroids in target cells. In the present work, expression of SHBG mRNA and CBG mRNA was demonstrated in tissues of human normal endometrium and pelvic endometriosis, using the reverse transcription-polymerase chain reaction (RT-PCR). SHBG mRNA levels were higher in pelvic endometriosis than in normal endometrium (P < 0.02), while CBG mRNA levels were lower than in normal endometrium (P < 0.05). The SHBG mRNA/CBG mRNA ratio was significantly higher in pelvic endometriosis than in normal endometrium (P < 0.01). These findings suggest that overexpression of intercellular SHBG in endometriotic tissues results in the formation of the estrogen-predominant milieu, since SHBG-bound estrogen is considered to be protected from the metabolism in liver and available in endometrial cells, thereby assisting the development of the pelvic endometriosis.

Adult↗

Plasma variation of corticosteroid-binding globulin and sex hormone-binding globulin.

Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) circulate in plasma and bind their cognate ligands with high affinity, offering a steroid delivery system to target tissues by a variety of mechanisms. Analysis of these steroid-binding proteins is gaining importance in the clinical setting, although more information is warranted on their diurnal and biological variation. This study shows that plasma SHBG (in normal subjects) exhibits little diurnal or biological variation over the 30 day period studied, in contrast to CBG, where plasma levels peak in the early afternoon. This leads to attenuation of the diurnal free cortisol level rhythm compared to total cortisol. We also show that plasma CBG is significantly lower in male subjects with the metabolic syndrome compared to age-matched lean counterparts, and may therefore act as a surrogate marker of insulin resistance. The consequence of lower levels of CBG in these obese male subjects is reflected by higher levels of circulating free cortisol, potentially offering a more favourable environment for adipogenesis.

Adult↗

Development of an intravenous gamma-globulin with Fc activities. I. Preparation and characterization of S-sulfonated human gamma-globulin.

S-sulfonated gamma-globulin (S-GG) was prepared by treating gamma-globulin with sulfite and tetrathionate ions. About four interchain disulfide bonds were selectively cleaved to give S-sulfonate groups. Although the above treatment strongly suppresses anticomplementary activity and nonspecific skin reactivity, the resulting S-GG retains high antibody activity. Furthermore, S-GG was found to maintain satisfactory levels for prolonged periods in vivo. The physicochemical and antigenic analyses of S-GG suggest that the S-sulfonation induces structural modification only at restricted sites.

Complement Fixation Tests↗

Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males.

AIM: Plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) may be regulated by insulin. The aim of this study was to test the hypothesis that these steroid-binding proteins are markers of insulin resistance and obesity in adult patients with the metabolic syndrome. METHODS: Fasting blood samples were obtained from 108 male and 88 female overweight adult patients who had varying degrees of dyslipidaemia, adiposity and insulin resistance. We measured plasma levels of SHBG and CBG and investigated their correlation with insulin resistance [homeostasis model assessment (HOMA) % sensitivity] and anthropometric markers of adiposity. RESULTS: In male patients, plasma SHBG correlated positively with HOMA (% sensitivity) and negatively with anthropometric measurements, including body mass index, waist circumference (cm) and percentage body fat. There was no correlation with CBG and any other parameter in the male patients. The female patients were treated as two groups, those not using oral contraceptives or hormone replacement therapy (n = 67) and those taking steroid medications (n = 21). Female patients using steroid medications had significantly higher SHBG levels but neither group showed any correlation between SHBG, insulin resistance and adiposity. Correlation studies of CBG with other parameters in the female subgroups did not reach statistical significance. CONCLUSIONS: We conclude that plasma SHBG is another surrogate marker for insulin resistance in obese males but not in obese females. It also appears that plasma CBG is not a useful marker of insulin resistance in patients with the metabolic syndrome.

Biomarkers↗

Comparison of serum ethinyl estradiol, sex-hormone-binding globulin, corticoid-binding globulin and cortisol levels in women using two low-dose combined oral contraceptives.

The study included 69 women taking a desogestrel (n = 30)- or gestodene (n = 39)-containing low-dose combined oral contraceptive for at least 3 months. Group size was calculated to detect a difference in mean values of 80% of 1 standard deviation (alpha = 0.05, beta = 0.1). Seven serum samples were obtained up to 4 h, and 1 sample 24 h, after drug intake on 1 day between the 10th and the 21st day of the cycle. The concentrations of sex-hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and cortisol were measured in a 0- to 4-hour serum pool by radioimmunoassay. Ethinyl estradiol (EE2) levels were analyzed in single and pooled samples using anti-EE2-6 beta-carboxymethyloxime-bovine serum albumin antiserum. The area under the curves (AUC) up to 4 and 24 h and Cmax and tmax were evaluated. Statistical analysis (analysis of covariance) did not reveal a dependence of values on duration of treatment or day of cycle. Both treatments resulted in almost identical values for all parameters evaluated. The mean levels of SHBG, CBG and cortisol were in the range of 186-226 nmol/l, 89-93 mg/l and 280-281 micrograms/l, respectively. Mean maximum EE2 levels of 106-129 pg/ml were found 1.6-1.8 h after pill intake and AUC0-4 h accounted for 329-374 pg.h.ml-1. The recently reported differences in serum EE2 and CBG levels between two groups of 11 women each treated with desogestrel- and gestodene-containing pills, respectively, could not be confirmed.

Adult↗

Expression of sex hormone-binding globulin and corticosteroid-binding globulin mRNAs in corpus luteum of human subjects.

To understand the biology of sex steroids in human ovarian corpus luteum, the expression of intracellular sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNAs as a manifestation of intracellular SHBG and CBG expression was determined. The expression of SHBG and CBG mRNAs was detected in all samples analyzed. Luteal SHBG mRNA level showed no significant change during the endometrial secretory phase of the menstrual cycle. On the other hand, luteal CBG mRNA level was significantly higher (p < 0.05) at the mid-secretory phase than that at the early and late secretory phases of the endometrium. These findings suggest that human ovarian corpus luteum synthesizes SHBG and CBG intracellularly, CBG being plausibly involved in the functional life span of corpus luteum.

Adult↗

Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under equilibrium conditions using a solid phase method at physiological pH and temperature. A computer program was used to solve the complex equilibrium interactions between these steroids and TeBG, CBG, and albumin. In this manner, we calculated the plasma distribution of each steroid into TeBG-bound, CBG-bound, albumin-bound, and unbound fractions in normal men, normal women during both the follicular and luteal phases of the ovarian cycle, and women during the third trimester of a normal pregnancy.

Adrenal Cortex Hormones↗