Serum Sex Hormone-binding Globulin Concentrations Research Articles

Lynestrenol induced therapeutic amenorrhea: effects of dose reduction on serum sex-hormones and lipids.

The effect of reducing the dose of peroral lynestrenol by half on serum sex-hormone, lipid and lipoprotein status was studied in 21 mentally retarded women with therapeutic amenorrhea (TA). They had previously received 5 or 10 mg peroral lynestrenol daily for periods ranging from 32 to 196 months. Dose halving of lynestrenol resulted in an increase in serum total testosterone (T) by 16% (p less than 0.05), sex-hormone binding globulin (SHBG) by 39% (p less than 0.01) and high-density lipoprotein cholesterol (HDL-C) by 28% (p less than 0.001). Both the mean serum total and free concentrations of norethisterone (NET and fNET) decreased by 60% (p less than 0.001). The serum concentrations of 17-beta-estradiol (E2), its free fractions (fE2) and free T (fT) were not significantly altered. Significant correlations were observed between the change in HDL-C and the change in T (r = 0.45, p less than 0.05), between the change in SHBG and the change in T (r = 0.62, p less than 0.01), fT (r = 0.43, p less than 0.05) and E2 (r = 0.51, p less than 0.05). The elevation of HDL-C was probably caused by the reduced serum NET concentrations. This also resulted in an increase in serum SHBG concentration, which is regarded as an indicator of the overall estrogen/androgen ratio.

Serum levels of free and bound testosterone in hyperthyroidism.

The aim of this study was to improve knowledge about the relationships between free and bound forms of testosterone in serum and the major testosterone-binding proteins during hyperthyroidism. Nine men and 11 women were studied when hyperthyroid due to Graves' disease and again after at least 3 months of euthyroidism. The serum concentrations of free T3, free T4, TSH, sex hormone-binding globulin (SHBG), LH, progesterone and free, non-SHBG bound and total testosterone were determined. For both sexes, hyperthyroidism was associated with significant elevations of the mean total testosterone and sex hormone-binding globulin (SHBG) levels and significant depressions of the mean percentage and concentration of non-SHBG-bound testosterone and the mean percentage of free testosterone. For women, the mean free testosterone concentration was significantly lower during hyperthyroidism than during euthyroidism; no significant difference in mean free testosterone concentration was observed between hyperthyroid and euthyroid men. When the experimentally derived data were analysed according to a model based on the binding constants of testosterone with SHBG and albumin, the simulated results for each patient when hyperthyroid and euthyroid paralleled the actual results. However, the model consistently overestimated the actual amounts of non-SHBG-bound testosterone. There was a significant correlation between SHBG concentration and the severity of thyrotoxicosis as measured by the change in thyroid hormone levels between euthyroidism and hyperthyroidism. Our results support the following pathogenetic sequence: thyrotoxicosis leads to a rise in serum SHBG concentration which is accompanied by an increase in testosterone concentration, a fall in the concentration of non-SHBG-bound testosterone and little or no change in the concentration of free testosterone.

Insulin resistance and Na+/K(+)-ATPase in hypertensive women: a difference in mechanism depending on the level of glucose tolerance.

1. The peripheral glucose disposal rate (assessed with the euglycaemic-hyperinsulinaemic clamp technique), the serum sex hormone-binding globulin concentration and total and ouabain-sensitive 22Na-efflux rate constants in leucocytes were determined in 41 women with impaired glucose tolerance and in 40 women with normal glucose tolerance. The groups were matched for body mass index and diastolic blood pressure (range 55-112 mmHg). 2. Stepwise regression analysis showed that diastolic blood pressure in the group with impaired glucose tolerance was inversely correlated with the glucose disposal rate (model r2 = 21%) and was correlated with the plasma glucose concentration at 120 min after an oral glucose load (model r2 = 31%). In the group with normal glucose tolerance, however, neither of these two variables was correlated with blood pressure, although the ouabain-sensitive 22Na efflux rate constant was (model r2 = 11%). 3. Among insulin-resistant subjects, those with hypertension had significantly lower serum sex hormone-binding globulin concentrations than the normotensive subjects. 4. We conclude that insulin resistance is correlated with high blood pressure in women with glucose intolerance and increased androgenic activity. In women with normal insulin sensitivity, a low level of the Na+/K(+)-ATPase-mediated sodium efflux is associated with high blood pressure.

The role of nutrition and insulin in the regulation of sex hormone binding globulin

In an analysis of 263 women with polycystic ovary syndrome (PCOS), 91 (35%) of whom were obese (body mass index > 25 kg/m 2), it was found that obese women with PCOS were more likely to be anovulatory and had a higher prevalence of hirsutism than the non-obese subgroup. Although serum concentrations of gonadotrophins, androstenedione and total testosterone were similar in obese and lean women with PCO, sex hormone binding globulin (SHBG) levels were significantly lower, and free testosterone correspondingly higher, in obese women. Serum concentrations of SHBG were inversely correlated with those of both fasting and glucose-stimulated insulin. A short-term, very-low-calorie diet resulted in a 2-fold increase in SHBG which was mirrored by a fall in serum insulin. Similar biochemical changes were also observed during a long-term (6–7 months) 1000 kcal diet and were associated with an improvement of menstrual function and fertility. This encourages the view that calorie restriction has an important part to play in the management of obese women with PCOS.

Low Sex-Hormone-Binding Globulin Concentration as Independent Risk Factor for Development of NIDDM: 12-Yr Follow-Up of Population Study of Women in Gothenburg, Sweden

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38-60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.

Bovine Steroid Hormone and SHBG Concentrations Postpartum and during the Oestrous Cycle

Changes in consecutive estimates of milk progesterone concentrations and serum steroid hormone and sex hormone-binding globulin (SHBG) concentrations in the postpartum period were examined in Finnish Ayrshire and Friesian dairy cows which were divided according to feeding into a hay group and a silage group. Milk progesterone concentrations rose above 10 nmol/l, indicating the start of ovarian luteal activity, slightly earlier in the silage group (28.4 +/- 8.7 (S.D.) days, n = 19) than in the hay group (33.4 +/- 10.3, n = 28) after calving. Likewise, the first normal oestrous cycles began slightly earlier in cows fed with silage. On the other hand, no differences in the beginning of ovarian luteal activity were observed between the breeds. Serum oestradiol-17 beta, oestrone, testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), pregnenolone and progesterone concentrations were fairly unchanged during postpartum anoestrus after uterine involution and before ovarian cyclic activity. After first ovulation, considerable increases in milk and serum progesterone concentrations were observed. The increase was accompanied by elevations in serum pregnenolone and 5 alpha-DHT concentrations. In the late luteal phase, progesterone, 5 alpha-DHT and pregnenolone concentrations rapidly declined, leading to low hormone levels in pro-oestrus. Thereafter, serum pregnenolone and 5 alpha-DHT concentrations slightly increased during the follicular phase. On the other hand, oestradiol-17 beta concentrations were elevated in pro-oestrus and decreased after that, being lowest at met-oestrous. Serum testosterone concentrations appeared to be unchanged during postpartum anoestrus and over the oestrous cycle. Serum SHBG concentrations were unchanged during postpartum anoestrus and over the oestrous cycle, as well as in pregnant animals. The serum SHBG concentrations were about double those found in women with normal menstrual cycles, whereas oestradiol concentrations were much lower. At present, it cannot be explained how the biological effects of oestradiol become evident under such conditions.

Changes in circulating hormone levels after ovarian wedge resection in patients with polycystic ovary syndrome

Serum gonadotropin, prolactin, estradiol, sex hormone binding globulin (SHBG) and androgen levels were measured before, 5 days and 6 weeks following ovarian wedge resection in 9 patients with polycystic ovary syndrome. Elevated levels of LH, androstenedione, testosterone and dehydroepiandrosterone-sulphate (DHEA-S) were found before surgery. There was a marked decrease in androstenedione and DHEA-S levels 5 days following wedge resection, but a rebound effect could be observed 6 weeks later. Serum gonadotropin, prolactin, testosterone and SHBG concentrations were practically unaffected by surgery. At 6-12 months follow up patients showed regular, mainly ovulatory cycles, but pregnancy occurred only in two cases.

Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood

Early menarche is a risk factor for breast cancer. In a longitudinal manner, we have investigated the endocrine features of girls with early menarche. This study extends our investigations to the third decade of life in a cohort of girls followed up for 13 years. The group studied comprised 44 women, 20-31 years of age. Eleven women had had their menarche before 12.0 years, 14 women at 12.0-12.9 years and 19 women at 13.0 years or more. The women who had had early menarche had higher serum oestradiol concentrations during the follicular phase of the menstrual cycle than the women who had had their menarche later. The serum oestradiol concentrations increased rapidly at the beginning of cycle in these "early menarche" women. If there is a threshold which serum oestradiol concentrations must exceed to increase the risk of breast cancer, then these women have more days at risk than other women. In addition, the serum SHBG (sex-hormone-binding globulin) concentration was about 30% lower in the follicular-phase specimens of the women who had had their menarche before 12.0 years compared with those who had had their menarche at 13.0 years. Our data therefore indicate that women with early menarche are subject to a high degree of oestrogen stimulation at least until approximately 30 years of age. Our findings may have important consequences for the design of intervention programs for breast cancer prevention.

Thyroxine uptake by human hepatoma cells from serum of patients submitted to long-term thyroxine suppressive therapy.

The significance of thyroxine (T4) uptake from serum in the assessment of thyroid status was evaluated, using human hepatoma (Hep G2) cells, in 30 euthyroid subjects, 6 hypothyroid and 19 hyperthyroid patients, and in 23 athyreotic cancer patients under T4 suppressive therapy. Cellular thyroxine (CT4) was determined according to Sarne and Refetoff, J. Clin. Endocrinol. Metab. 61: 1046, 1985. CT4 averaged 9.9 +/- 2.8 pg/well (mean +/- SD, range 5.7-15.3) in euthyroid subjects, 1.5 +/- 1.0 pg/well (range 0.05-4.2) in hypothyroid patients, 40.5 +/- 18.8 pg/well (range 18.3 +/- 104.7) in hyperthyroid patients, and 23.7 +/- 7.2 pg/well (range 14.2-40.2) in T4-treated patients. In eu-, hypo- and hyperthyroid patients, a significant correlation was observed between CT4 and free T4 index (FT4I), free T4 (FT4) or Sex Hormone Binding Globulin (SHBG) values. In T4-treated patients, CT4 values were correlated with FT4I values, but not with FT4 or SHBG levels. All T4-treated patients with elevated SHBG levels had elevated FT4, FT4I and CT4 values. In contrast, of the 16 T4-treated subjects with normal serum SHBG concentrations, all but one had normal FT3, 3 (19%) had elevated FT4, 10 (62%) elevated FT4I and 13 (81%) elevated CT4, but all (100%) had undetectable TSH levels. Thus, considering serum SHBG concentrations as a parameter of hepatic tissue response to thyroid hormone, CT4 values, at least in T4-treated patients, do not accurately reflect the liver responsiveness to thyroid hormone action.

Interactions of contraceptive steroids with binding proteins and the clinical implications.

There are various complex interactions between combined oral contraceptives (COCs) containing the estrogen, ethinyl estradiol, and a synthetic gestagen and sex hormone binding globulin (SHBG). 1 interaction is that the magnitude of effect of the COC on hepatic synthesis, and thus serum concentration of SHBG, depends on the relative doses of the estrogen and gestagen and on the nature of the gestagen. Next, the interaction between the COC and the SHBG affects the biological activity of the synthetic steroids and influences the binding and the biological activity of the sex hormones produced by the body. The extent of this effect is based on the relative doses of the estrogen and gestagen, on the nature of the gestagen, and the concentration of endogenous sex hormones present. In addition, since women take the COC once/day, serum concentrations of the synthetic estrogen and gestagen fluctuate. Therefore the equilibrium between the synthetic hormones and the endogenous sex hormones also changes. Finally, a broad variation exists in serum concentrations of the synthetic estrogen and gestagen between females using the same COC. Therefore large intersubject variations between SHBG and the endogenous and exogenous hormones are expected.

Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration.

Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS)

Time-resolved immunofluorometric assay of sex-hormone binding globulin.

A time-resolved immunofluorometric assay (trlFMA) for human sex-hormone binding globulin (SHBG) is described in which antibody-coated tubes or microliter strip-wells and a europium (Eu) chelate-labeled monoclonal antibody are used. The trlFMA sensitivity is similar to that of other SHBG immunoassays, and other analytical variables compare favorably with an SHBG immunoradiometric assay (IRMA) kit and a steroid binding capacity assay: the interassay coefficient of variation (CV) is less than 8% and the intra-assay CV is less than 6% for concentrations between 6 and 200 nmol/L. The reference intervals (means +/- SD) for SHBG concentrations (nmol/L) in serum from 10 men, 10 women, and 10 pregnant women were 23 +/- 12, 65 +/- 39, and 439 +/- 122, respectively. In 14 hirsute women the mean +/- SD serum SHBG concentration (37 +/- 21 nmol/L) was significantly lower (P less than 0.01) than the mean for an age-matched, nonhirsute female comparison group. The trlFMA is technically simple, requires no centrifugation or separation reagent, and takes a counting time of only 1 s. In addition, the Eu-label is nontoxic, presents no waste-disposal problems, and has a long shelf life.

High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment.

We measured serum sex hormone-binding globulin (SHBG), total testosterone (T), non-SHBG-bound T, albumin-bound T, free T, and SHBG-bound T in 19 prepubertal boys with hypopituitarism. Serum SHBG decreased with age with a slope similar to that in 91 normal prepubertal boys at higher level, and therefore, it reached similar values at a later age. Serum SHBG was significantly higher in hypopituitary prepubertal boys [mean, 123 +/- 12 (+/- SE) nmol/L] than in normal prepubertal boys (76 +/- 4; P less than 0.001) despite the fact that their mean age was also higher (10.0 +/- 4 vs. 7.1 +/- 4.1 yr; P less than 0.001). In 4 boys with isolated hypogonadotropic hypogonadism (Kallman's syndrome), aged 15.6 +/- 1.5 yr, serum SHBG was 21 +/- 14 nmol/L, a value below the 95% confidence limit of the regression line in GH-deficient boys. The affinity constants of association of the SHBG-DHT complex were similar in hypopituitary and normal boys. Eleven of the 19 hypopituitary boys (mean chronological age, 8.3 +/- 2.5 yr; mean bone age, 4.1 +/- 2.1 yr) were treated with recombinant hGH (0.5 U/kg BW.week) for 1 yr. Their mean serum SHBG level before treatment was 154 +/- 14 nmol/L, and it decreased gradually to 106 +/- 5 nmol/L (P less than 0.01) after 12 months of treatment. The tendency toward normalization of serum SHBG during treatment suggested that GH deficiency was responsible for the high serum SHBG levels. Serum SHBG correlated negatively with age in both treated hypopituitary and normal boys, but the slope of the regression line was significantly steeper in treated hypopituitary boys (P less than 0.01). On the other hand, the mean serum non-SHBG-bound T level was 0.10 +/- 0.02 (+/- SE) nmol/L in hypopituitary boys, significantly lower than that in normal boys (0.21 +/- 0.02 nmol/L; P less than 0.02). Since serum total T concentrations were similar in the two groups, the higher serum SHBG concentration resulted in lower serum bioavailable T levels in the hypopituitary boys. These changes might explain the poor response to T treatment reported in GH-deficient patients. The lower serum non-SHBG-bound T concentrations in the GH-deficient boys suggest there may be delayed exposure of central nervous system structures to increased levels of sex hormones, which, in turn, may slow body maturation. This mechanism might play a role in the delay of puberty that occurs in patients with isolated GH deficiency.

Serum Sex Hormone—Binding Globulin in Amiodarone-Treated Patients

The lodinated antiarrhythmic drug amiodarone frequently causes an elevation of the serum thyroxine (T4) level in patients who remain clinically euthyroid. Less frequently, true iodine-induced hyperthyroidism may occur. The clinical and laboratory distinction between these two conditions is often difficult. Since the serum sex hormone-binding globulin (SHBG) concentration is elevated in hyperthyroidism, this study was carried out to evaluate the serum SHBG concentration as a possible marker of hyperthyroidism in patients receiving amiodarone. Patients treated with amiodarone were divided into three groups: clinically euthyroid with normal serum T4 and triiodothyronine (T3) concentrations, clinically euthyroid with elevated serum T4 and normal T3 concentrations, and clinically hyperthyroid with elevated serum T4 and T3 concentrations. The mean serum SHBG concentration was significantly elevated in amiodarone-induced hyperthyroid patients, while it was normal in euthyroid patients treated with amiodarone who had normal or elevated serum T4 concentrations. The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated.

Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients.

Factors affecting TSH suppression by L-T4 administration were retrospectively evaluated in 452 patients: 180 who were athyreotic after total thyroidectomy and remnant radioiodine ablation for differentiated thyroid carcinoma and 272 with nontoxic diffuse or nodular goiter. All patients were considered clinically euthyroid. TSH secretion was assessed by iv TRH stimulation testing. The T4 dose associated with an undetectable basal serum TSH level and no increase in serum TSH after TRH administration (suppressive dose) averaged 2.7 +/- 0.4 (SD) micrograms/kg body weight (BW)/day in athyreotic patients and 2.1 +/- 0.3 micrograms/kg BW/day in goitrous patients (P less than 0.001). The 25th-75th percentile intervals were 2.5-2.9 micrograms/kg BW/day for athyreotic patients and 1.9-2.3 micrograms/kg BW/day for goitrous patients. The suppressive dose of T4 was dependent in both groups on patient age, younger patients needing higher doses than older patients. The duration of treatment also proved to be an important parameter, since in both groups the percentage of patients with suppressed TSH secretion increased if TRH testing was carried out after at least 6 months after the initiation of therapy. Serum total T4, total T3, free T3 (FT3), free T4 (FT4) index, and FT3 index values did not differ in the two groups and were significantly higher (P less than 0.001) than in normal subjects. Mean serum FT4 was significantly higher in athyreotic patients than in goitrous patients with suppressed TSH secretion. Among athyreotic patients with suppressed TSH secretion, 24% had elevated serum FT4 and FT3, and 47% had elevated serum FT4 alone. Of goitrous patients with suppressed TSH secretion, 20% had elevated serum FT4 and FT3, and 27% had elevated serum FT4 alone. On the other hand, 35% of athyreotic patients and 14% of goitrous patients whose TSH secretion was not suppressed had elevated serum FT4. Serum sex hormone-binding globulin concentrations were measured in 3 groups of goitrous women. Values above normal limits were found in 13/26 patients (50%) with high serum FT4 and FT3, in 4/30 patients (13%) with elevated serum FT4 alone, and in 1/25 patients (4%) with normal FT4 and FT3. TSH suppression requires daily doses of T4 between 2.5 and 2.9 micrograms/kg BW in athyreotic patients and between 1.9 and 2.3 micrograms/kg BW in goitrous patients, with appropriate adjustments in relation to the age of the patient; Assessment of the adequacy of treatment should not be carried out before 6 months after the institution of therapy.

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 K a 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.

A method for the determination of sex hormone binding globulin in human serum

A simple and rapid method for serum sex hormone binding globulin (SHBG) was developed. Sera from pregnant women were pooled and the SHBG concentration was measured by Rosner's method. This pool was diluted with charcoal-treated and heated serum to give standards ranging in concentrations from 26.8-0.8 micrograms/L. Two sets of tubes containing dihydrotestosterone (DHT), assay and control tubes, were prepared. Diluted standards and unknowns were added to assay and control tubes along with tritiated DHT. Following incubation, cold saturated ammonium sulfate was added to each tube, mixed, centrifuged and the supernatant counted. Mean SHBG concentration (microgram/L +/- SEM) in normal men was 3.6 +/- 0.4, normal women 11.4 +/- 2.2, pregnant women 58 +/- 2.6, obese women 3.3 +/- 1.0, hirsute women 2.9 +/- 0.2, hypothyroid women 7.3 +/- 1.0, and hyperthyroid women 26.0 +/- 1.6. These results correlate well with previous reports. This method is fast, convenient, and up to 40 samples can be analyzed in one assay.

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 < 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.

Serum sex hormone-binding globulin during puberty in girls and in different types of adolescent menstrual cycles.

Serum sex hormone binding globulin (SHBG) concentrations were measured by an immunoradiometric assay, as part of a longitudinal study of puberty in girls, and were related to age, pubertal stage, age at menarche, weight, nature of the menstrual cycle and serum concentrations of sex steroids. A slow but very significant decrease was seen in SHBG from 77 nmol/l at 8-10 years of age to about 50 nmol/l after 15 years of age. Serum SHBG concentrations showed weak negative correlations with those of androstenedione and testosterone during puberty. The closest associations found between SHBG and the parameters measured were negative correlations with weight and body fat percentage in both pre-menarcheal and post-menarcheal girls, even after the effect of age was accounted for by calculating partial correlation coefficients. Girls who experienced early menarche (before 13.0 years) had lower SHBG but higher oestradiol serum concentrations at 10.0-15.9 years of age compared to girls with later menarche. In ovulatory menstrual cycles, a significant increase in SHBG was found from the early to the late part of the cycle, whereas no changes took place in anovulatory cycles. Serum concentrations of SHBG showed positive correlations with those of oestradiol and progesterone in specimens taken in the late part of the cycle. In view of the weak relationships between serum SHBG and sex steroid concentrations, and the strong relationships between SHBG, weight and body fat percentage, factors other than steroids have to be considered in the regulation of SHBG levels during puberty.

The effect of D- and L-thyroxine on sex hormone-binding globulin in rabbits.

Serum sex hormone-binding globulin (SHBG) concentration is increased in patients with thyrotoxicosis. SHBG is also present in rabbit serum, although it does not bind estradiol-17 beta (E2). Studies were carried out in female rabbits to determine the effects of thyroid hormone on SHBG. Serum concentrations of L-T4 cholesterol, E2, progesterone, free and total testosterone (T), and SHBG were measured in immature female rabbits (8-10 weeks of age). Rabbits were ovariectomized or subjected to sham surgery at puberty (age, 14-16 weeks) and restudied 6 weeks later. Values for serum T4, T, percent free T, free T, E2, progesterone and cholesterol were similar in ovariectomized and sham treated rabbits. Serum SHBG concentration progressively decreased in all rabbits from immaturity to age 20-22 weeks and values remained constant thereafter. Ovariectomy did not affect this age-related decrease in serum SHBG concentration. The 20- to 22-week-old ovariectomized and sham-operated rabbits were treated daily with either 30 micrograms/kg L-T4 or 150 micrograms/kg D-T4 for 2 weeks. This dose of L-T4 induced a 10-25% loss of BW, whereas D-T4 treatment did not, strongly suggesting that the L-T4 but not the D-T4-treated rabbits were hypermetabolic. D-T4 and L-T4 induced similar increases in serum SHBG (D-T4, delta 132 nM; L-T4, delta 146 nM). The increase in serum SHBG activity in response to D-T4 or L-T4 was reversible, since serum SHBG concentration returned to pretreatment values 5 weeks after thyroid hormone therapy was discontinued. The 27- to 29-week-old rabbits were then treated for 2 weeks with D-T4 (150 micrograms kg-1 day-1). Serum SHBG concentration significantly increased, and there were negative correlations between the thyroid hormone-induced increase in SHBG activity and both the percent free T and free T (P less than 0.01). D-T4 administration significantly lowered the serum cholesterol concentration without altering BW.