Binding Globulin Research Articles

Fasting induces the generation of serum thyronine-binding globulin in Zucker rats.

Five-month-old lean and obese Zucker rats were fasted for up to 7 days (lean rats) or 28 days (obese rats), and serum total and free T4 and T3 concentrations, percent free T4 and T3 by equilibrium dialysis, and the binding of [125I] T4 to serum proteins by gel electrophoresis were measured. In the lean rats, a 4- or 7-day fast resulted in significant decreases in serum total and free T4 and T3 concentrations. There was a decrease in the percent free T3 after 7 days of starvation. In contrast, a 4- or 7-day fast did not alter any of these variables in the obese rats. However, after 14 or more days of starvation, serum total T4 and T3 concentrations increased, and the percent free T4 and T3 decreased, resulting in no change in the serum free T4 or T3 concentrations in the obese rats. The percent of [125I]T4 bound to serum thyronine-binding globulin increased and the percent bound to thyronine-binding prealbumin decreased with the duration of the fast in both the lean and obese rats. The increase in serum thyronine-binding globulin binding of T4 can explain the increase in serum total T4 and T3 concentrations, the decrease in percent free T4 and T3, and the normal free hormone concentration in the long term fasted obese rats. The findings in the lean rats appear to be due to a combination of the known central hypothyroidism that occurs during 4-7 days of fasting and the fasting-induced changes in T4 binding in serum. Changes in T4 and T3 binding in serum during fasting in the rat must be considered when the effects of fasting on serum concentrations of the thyroid hormones, thyroid hormone kinetics, and the peripheral action of the thyroid hormones are evaluated.

Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol

The pronounced hepatic impact of oral ethinyl estradiol has been attributed by some to its so-called first-pass effect through the liver as only some 40% of ingested ethinyl estradiol reaches the systemic circulation. Others believe that ethinyl estradiol exerts its hepatic effects of its chemical composition, specifically its 17α-ethinyl group. In an attempt to resolve this controversy, a study was undertaken to determine whether vaginal administration of ethinyl estradiol can selectively reduce the hepatic effects of oral ethinyl estradiol. To compare the effects of oral and vaginal ethinyl estradiol, a group of postmenopausal subjects received either 5 μg of oral and 20 μg of vaginal ethinyl estradiol or 10 μg of oral and 50 μg of vaginal ethinyl estradiol in either sequence, respectively. Oral ethinyl estradiol was four to five times more potent than vaginal ethinyl estradiol. The potency ratios of the oral-vaginal ethinyl estradiol doses required to suppress follicle-stimulating hormone and luteinizing hormone were 4.4 and 3.2 and those to raise sex hormone-binding globulin binding capacity, corticosteroid-binding globulin binding capacity, and high-density lipoprotein cholesterol as well as lower low-density lipoprotein cholesterol were 3.5, 5.0, 4.2, and 4.2, respectively. These essentially equal oral-vaginal route potency ratios for both central nervous system and hepatic effects indicate that vaginal administration of ethinyl estradiol does not selectively reduce its hepatic impact in relation to its central nervous system effects. The pronounced hepatic effects of ethinyl estradiol are therefore attributed to its chemical composition.

The interaction between sex hormone binding globulin and levonorgestrel released from vaginal rings in women

The levels of levonorgestrel (L-NOG), progesterone and estradiol were measured in plasma samples of 17 normally menstruating women during a control cycle and during a subsequent period (90 days) with a L-NOG-releasing vaginal ring. During days 38–66 after the insertion of the vaginal ring the concentrations of sex hormone binding globulin binding sites (hereafter: SHBG levels) were also assayed. Significant correlations were found not only between the corresponding levels of SHBG and L-NOG during exposure to the latter compound (r = 0.44; P < 0.05), but also between the levels of SHBG in the control cycle and the levels of L-NOG measured during exposure (r = 0.60; P < 0.01). Furthermore, the decrease in SHBG levels during the vaginal administration of L-NOG was directly proportional to the levels of SHBG in the pretreatment cycle (r = 0.64; P < 0.01). A significant relationship was found between the levels of L-NOG (and, hence — indirectly — the levels of SHBG) and the degree of suppression of ovarian function. Thus the levels of L-NOG were lower (P < 0.01) in the subjects (n = 8) with an apparently normal or partially suppressed ovulatory-like pattern of progesterone than in those subjects (n = 9) in whom progesterone levels were completely suppressed.

Serum concentration of unsaturated thyroxine-binding globulin in hyper- and hypothyroidism.

The concentration of serum thyroxine (T4)-binding globulin (TBG) not binding T4 (unsaturated TBG, u-TBG) was determined in hyper- and hypothyroidism. u-TBG was expressed as the product of TBG concentration and the ratio of free TBG capacity to maximal TBG capacity as determined by reverse-flow electrophoresis. u-TBG concentration in normal sera (n = 40) was 15.5 +/- 2.3 mg/l (mean +/- SD), or 257 +/- 38 nmol/l for a molecular weight of TBG of 60 000 daltons. u-TBG levels were significantly lower in hyperthyroidism (7.1 +/- 2.3 mg/l, n = 16, P less than 0.001) and higher in hypothyroidism (21.7 +/- 5.0 mg/l, n = 22, P less than 0.001). Based on partial correlation analysis, u-TBG was inversely correlated to serum T4 (r = -0.586, P less than 0.001), but not correlated to triiodothyronine (T3) (r=-0.180, NS). There was a reciprocal correlation between u-TBG concentration and the T3 uptake value (r = 0.748, P less than 0.001). There was also a reciprocal correlation of u-TBG with both % free T4 (r = 0.425, P less than 0.001) and % free T3 (r = 0.377, P less than 0.001), when the data were subjected to partial correlation analysis. These results provide the values for u-TBG concentration in hyper- and hypothyroidism, and support the concept that the free fractions of serum thyroid hormones may be determined by the number of binding sites of the TBG molecule that are not saturated with T4 in hyper-and hypothyroidism.

Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males.

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.

Serum, total/free testosterone and sex hormone binding globulin binding capacity (SHBG) in a non-competitive marathon run.

Serum, total/free testosterone and sex hormone binding globulin binding capacity (SHBG) in a non-competitive marathon run.

Endocrine effects of danazol in the treatment of endometriosis.

The effects of danazol therapy on circulating gonadotrophins, oestradiol and sex hormone-binding globulin (SHBG) binding capacity have been studied in eight patients with endometriosis. There was a significant rise in luteinizing hormone (LH) in the first week of treatment with a fall in oestradiol levels. There was a marked fall in SHBG in the first week which continued up to 4 weeks. It is concluded that danazol is not 'anti-gonadotrophic' as frequently claimed and that its therapeutic actions, side effects and the endocrine changes could be explained by an effect on SHBG production. The rationale of its use in other conditions requires reconsideration.

The effect of progesterone administration on sex hormone binding globulin binding capacity in women with severe premenstrual syndrome

Thirty-one women with severe premenstrual syndrome had low sex hormone binding globulin (SHBG) binding capacities 30.2 ± 9.4 nmol DHT bound/1. The SHBG binding capacities rose when they were treated with three different doses of progesterone. On 400 mg (17 women) SHBG level was 45.11 ± 11.80. On 800 mg (8 women) SHBG binding capacity rose to 64.75 ± 14.30 and on the six women who took 1200 mg progesterone daily SHBG binding capacity was 78.5 ± 23.10. These results are discussed.

Anti-immunoglobulins and their idiotypes: are they part of the immune network?

The anti-gamma globulins represent a very heterogeneous group of proteins with widely different specificities that might be considered a portion of the immune network. The hypothesis is presented that at least some of these proteins have other specificities, with the anti-gamma globulin reactivity being a secondary property. Anti-idiotypic antibodies are possible candidates. This is based on the low binding affinity for gamma globulin of many of these proteins and the results of CRI and sequence studies. All the proteins of the major CRI group have VKIIIb light chains, and these have a dominant but not total influence on this CRI. This has been evident from studies with rabbit antibodies and recently also with monoclonal hybridoma antibodies. Sequence studies have also demonstrated the similarity in light chains that, however, are not greater than with other VKIIIb chains; the heavy chains show little similarity except possibly in the J segment. The possibility is discussed that antibodies with secondary anti-gamma globulin binding properties might have selective advantages.

Plasma Estradiol, Free Testosterone, Sex Hormone Binding Globulin Binding Capacity, and Prolactin in Benign Prostatic Hyperplasia and Prostatic Cancer

The nature of hormonal changes with age and the possible role of these changes in the development of benign prostatic hyperplasia (BPH) and prostatic cancer (PC) were studied by assaying the plasma levels of total and free testosterone (T), estradiol (E2), prolactin, and sex hormone binding globulin binding capacity (SHBG) in 20 normal healthy men aged 40-59 years, in 30 patients with BPH aged 63-79 years, and in 30 patients with PC of similar height, weight, and age as the BPH patients. The mean E2 was highly significantly (P less than 0.0005) lower in the PC patients and in the young controls than in the BPH patients. The mean free T was significantly higher in the young controls than in the BPH patients (P less than 0.025) and PC patients (P less than 0.0005). The PC patients had a slightly lower (P less than 0.05) mean free T and mean E2/free T ratio than the BPH patients. The mean E2/free T ratio was significantly higher in the BPH patients (P less than 0.0005) and in the PC patients (P less than 0.0025) than in the young controls. It seems possible that the observed age-dependent significant increase in plasma estrogen concentration in the BPH patients may act as a protective factor against prostatic cancer.

Genetic studies of Gc (vitamin D binding globulin) polymorphism in the population of Latium (Italy)

A group of 1235 unrelated Italians from four provinces of Latium were examined for Gc (group specific component) using isoelectric focusing. Types and frequencies of the Gc alleles were compared with thosc found in some other populations. A relatively large heterogeneity of this gene occurs even within a single region.

A versatile method for the determination of serum cortisol binding globulin and sex hormone binding globulin binding capacities

Cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) are plasma glycoproteins which bind some of the most important steroid hormones in blood with high affinity and specificity, but limited capacity. Although antisera have been raised against purified preparations of these proteins and radioimmunoassays have been developed to measure their actual serum concentrations [ 1,2], determinations of their steroid binding capacities will continue to be of importance, especially if variants with abnormal steroid binding activities exist [3,4]. In general, most methods currently used to determine the serum or plasma binding capacities of CBG and SHBG yield values which are in close agreement [5,6]. However, some of these methods are not suited for the routine analysis of large numbers of samples [7,8] while others require the use of expensive gels [9,10], or work under cold room conditions [ 111. Ammonium sulphate precipitation is probably the most widely used method to determine serum SHBG binding capacity [ 12141, but this technique is not so easily applied for measurement of CBG binding capacity, and cannot be readily adapted to measure SHBG binding capacity in samples containing low concentrations of protein, such as obtained during purification procedures. It has been our intention therefore to develop a reliable, inexpensive, versatile method that is suitable for the routine determination of both CBG and SHBG in dilute serum samples.

Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism

The first objective of this study was to determine which plasma androgen assay or combination of assays would be the most useful in documenting hyperandrogenism in women with hirsutism, acne, oligomenorrhea, or unexplained infertility. Plasma levels of androstenedione (A), total testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured and free T (FTc) was calculated from the measured total T and T-estradiol-binding globulin binding capacity (TeBG-BC) in 138 consecutive women referred to our clinic for hirsutism, acne, oligomenorrhea, and/or unexplained infertility. FTc was elevated in 82% and was most frequently elevated parameter. DHEAS was elevated in 59% of the women, and 93% were noted to have hyperandrogenemia on the basis of a combination of FTc and DHEAS levels. The second objective of this study was to determine whether there was significant correlation between the androgen parameters and any of the clinical features. Body weight was significantly negatively correlated with DHEAS and TeBG-BC in those women with a normal DHEAS level but not in those with an elevated level. A strong positive correlation (simple and partial) was noted between body weight and plasma T levels in the whole group of patients, as well as in those with a normal or an elevated DHEAS level. It is suggested that the relationship between T and body weight is multifaceted. Conceivably, T could influence body mass by effects on food intake or through alterations in intermediary metabolism.

Binding capacity of testosterone-estradiol-binding globulin (TeBG), total and calculated unbound concentrations of testosterone in patients with carcinoma of the prostate treated with orchidectomy or estrogens.

Testosterone-estradiol-binding globulin (TeBG) binding capacity, total estradiol-17 beta and total testosterone were measured in patients with carcinoma of the prostate treated with orchidectomy or estrogens. Comparisons were made with a control group. There was a significant increase in TeBG binding capacity in the group treated with estrogens. Both orchidectomy and estrogen-treatment decreased total testosterone significantly and to the same degree. The concentration of free testosterone was calculated using a new method, and was found to be lower in orchidectomized and estrogen treated patients when compared with the control group. When the two groups under treatment were compared, the calculated free testosterone concentration was significantly lower in the estrogen treated group.

Normalization of androgen and sex hormone-binding globulin levels after treatment of hyperprolactinemia.

Twenty-eight women with amenorrhea, galactorrhea and hyperprolactinemia without hirsutism were studied before and after bromocriptine therapy for 2 months. Compared to 15 euprolactinemic controls, hyperprolactinemic women had elevated levels of dehydroepiandrosterone sulfate and androstenedione and lower levels of total testosterone (T), and androst-5-ene-3 beta, 17 beta-diol (Adiol), and 17 beta-estradiol (P less than 0.05). Unbound T and unbound Adiol were significantly elevated, while sex hormone-binding globulin binding capacity was decreased (P less than 0.05) and corticosteroid-binding globulin binding capacity was normal. After treatment with bromocriptine, dehydroepiandrosterone sulfate and androstenedione decreased to control levels, as did unbound Adiol, while 17 beta-estradiol and sex hormone-binding globulin binding capacity levels increased significantly (P less than 0.05). Five hyperprolactinemic women underwent ACTH stimulation tests before and after treatment, and the results were compared to those of seven controls. Steroid ratios in response to ACTH suggested normal 3 beta ol-dehydrogenase-isomerase, 17-20-desmolase and 17 beta-hydroxysteroid dehydrogenase enzymatic activities in hyperprolactinemia. Basal steroid ratios of T to 5 alpha-androstane-17 beta-01-3-one) (DHT) and of unbound T to unbound dihydrotestosterone were elevated (P less than 0.05), suggesting reduced 5 alpha-reductase activity in hyperprolactinemia which is normalized after treatment. Hirsutism was not present in these patients with hyperprolactinemia despite elevated levels of unbound T and Adiol, and may be explained by reduced 5 alpha-reductase activity. Our data suggest that the increased levels of androgens in these patients result from the hyperprolactinemia.

A challenge of several concepts of free thyroxin index for assessing thyroid status in patients with altered thyroid-binding protein capacity.

I compared values for the free thyroxin index derived from data obtained by four triiodothyronine-uptake kits for 93 euthyroid subjects with normal or altered thyroxin-binding globulin binding capacity. In addition, I devised a mathematical model of an "ideal" free thyroxin index. Only one uptake kit satisfactorily normalized values for the free thyroxin index in the increased thyroglobulin groups, as compared with the control. The other three demonstrated contrasting patterns of free thyroxin index variation as compared with normal, when thyroglobulin concentrations were increased. By all four uptake tests, values for the free thyroxin index in thyroglobulin-deficient patients were significantly lower than normal. Values derived from one uptake kit behaved similarly to those of the "ideal" model. The failure of the free thyroxin index to compensate for increases in thyroglobulin concentration is therefore a function of specific uptake methods rather than a characteristic of free thyroxin index per se. However, the free thyroxin index is not a true reflection of thyroid status in patients with thyroglobulin deficiency. The model suggests that a curvilinear relationship between triiodothyronine uptake and the concentration of thyroxin-binding globulin can result in a free thyroxin index that corrects for increases in thyroglobulin binding capacity.

Plasma estradiol, free testosterone, sex hormone binding globulin binding capacity, and prolactin in benign prostatic hyperplasia and prostatic cancer.

The nature of hormonal changes with age and the possible role of these changes in the development of benign prostatic hyperplasia (BPH) and prostatic cancer (PC) were studied by assaying the plasma levels of total and free testosterone (T), estradiol (E2), prolactin, and sex hormone binding globulin binding capacity (SHBG) in 20 normal healthy men aged 40-59 years, in 30 patients with BPH aged 63-79 years, and in 30 patients with PC of similar height, weight, and age as the BPH patients. The mean E2 was highly significantly (P less than 0.0005) lower in the PC patients and in the young controls than in the BPH patients. The mean free T was significantly higher in the young controls than in the BPH patients (P less than 0.025) and PC patients (P less than 0.0005). The PC patients had a slightly lower (P less than 0.05) mean free T and mean E2/free T ratio than the BPH patients. The mean E2/free T ratio was significantly higher in the BPH patients (P less than 0.0005) and in the PC patients (P less than 0.0025) than in the young controls. It seems possible that the observed age-dependent significant increase in plasma estrogen concentration in the BPH patients may act as a protective factor against prostatic cancer.

The Effects of Forced Molt Treatment on Selected Steroids in Hens

A study was conducted to determine the effects of an environmentally induced forced molt on concentrations of plasma progesterone (P), corticosteroids (CS), corticosterone binding globulin binding capacity (CBGBC), and liver corticosteroids (LCS) during early forced molt.Laying hens were placed into two environmental control chambers. In one chamber, control (C) hens were fed ad libitum and maintained on long photoperiods of 19 hr of light daily to maintain egg production. In the other chamber, early forced-molt (EM) hens were exposed to short photoperiods of 6 hr of light daily to decrease egg production. After 2 weeks of ad libitum feeding, feed was withdrawn from the EM hens for 2 days to initiate a molt. Feed was restored for 3 days to the EM hens before hens from both groups were sacrificed every 2 hr for 2 days.The EM hens had regressed ovaries, greater body weight losses, lower plasma P and CS hormone levels, lower nuclei free LCS levels, and lower CBGBC than C hens. Nuclear LCS levels were similar in EM and C hens.A single peak indicating a daily rhythm of plasma P was found only in C hens. Progesterone secretions appeared to be eposodic in EM hens.A daily rhythm with two peaks of plasma CS and nuclei-free LCS was found in the C hens. Nuclear LCS peaked thrice daily in C hens. A cascade of CS from the plasma to the liver cytosol and on to the liver nucleus was indicated. Plasma CS was negatively correlated with nuclei-free LCS.Two daily peaks of plasma CS occurred in EM hens. One peak exhibited a daily rhythm and the other did not. Daily rhythmic peaks in EM hens were less defined than in C hens. Force molt treatment in EM hens may have affected the loss of the LCS peaks as was found in the C hens. No daily rhythms of CBGBC were found in either hen group.

The nature of big plasma somatostatin: Implications for the measurement of somatostatin-like immunoreactivity in human plasma

Big plasma somatostatin (BPS) represents an artifact of measurement. High-molecular-weight globulins (α, β, and γ) in human plasma inhibit, in a concentration-dependent manner, the binding of radiolabeled somatostatin analogs to antibody directed against somatostatin. The magnitude of inhibition varies with antibody and plasma sample and is greatest for the α-globulin fraction. The mechanism of inhibition involves binding of plasma globulins to antibody, thereby blocking tracer-binding sites, and does not involve inhibition by somatostatin bound noncovalently to plasma proteins or tracer degradation. Thus BPS arises from a property of plasma rather than of somatostatin and so it is suggested that this mechanism may account for the presence of other “big” forms of hormones in plasma.

Thyroid function in children with cystic fibrosis

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls. As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.