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Relations between sex hormones, sex hormone binding globulin, insulin-like growth factor-I and insulin-like growth factor binding protein-1 in post-menopausal breast cancer patients.

OBJECTIVE: Oestrogens, androgens and anti-endocrine drugs such as tamoxifen and aminoglutethimide influence plasma insulin-like growth factor-I (IGF-I). IGF-I, in turn, has been found to stimulate the peripheral aromatase in vitro. The aim of this study was to examine relations between sex hormones, IGF-I and insulin-like growth factor binding protein-1 (IGFBP-1) in post-menopausal women with breast cancer. DESIGN: To measure plasma sex steroids, sex hormone binding globulin (SHBG), IGF-I, IGFBP-1, insulin and urinary oestrogen metabolites in post-menopausal women with breast cancer not receiving any endocrine therapy. PATIENTS: Thirty-two patients had fasting blood samples obtained between 0800 and 1000 h. A sub-group of 10 patients had 24-hour urine oestrogen metabolites determined. MEASUREMENTS: Plasma steroids and proteins were measured by radioimmunoassays. Urinary oestrogens were measured by GC-MS. RESULTS: SHBG correlated negatively with plasma androstenedione (P < 0.001), insulin (P < 0.001), IGF-I, height and plasma oestrone sulphate (P < 0.025 for all), but positively with plasma IGFBP-1 (P < 0.025). IGFBP-1 correlated negatively with IGF-I (P < 0.001) and the testosterone/SHBG ratio (P < 0.05). Neither IGF-I nor IGFBP-1 correlated with any of the plasma or urinary sex hormones or with the oestrone/androstenedione and oestradiol/testosterone ratios. Multivariate analysis revealed plasma SHBG to correlate positively with IGFBP-1 (P = 0.029) and negatively with insulin (P = 0.031). Plasma IGFBP-1 correlated negatively with IGF-I (P < 0.0001) but not with insulin. CONCLUSION: Our results do not suggest any influence of plasma sex steroids in physiological concentrations on IGF-I or IGFBP-1 in post-menopausal breast cancer patients, nor do they indicate IGF-I at physiological concentrations influences the ratios between plasma oestrogens and their androgen precursors.

Aged↗

Interrelation between umbilical cord serum sex hormones, sex hormone-binding globulin, insulin-like growth factor I, and insulin in neonates from normal pregnancies and pregnancies complicated by diabetes.

Insulin concentration correlates negatively with sex hormone-binding globulin (SHBG) in adults, although the age at which this relationship develops is unknown. The present study assesses this relationship in a cohort of European, Maori, South Asian, and Pacific Islands neonates from 125 normal and 35 pregnancies complicated by diabetes. Maternal glycemia was assessed with a 3-h 100-g oral glucose tolerance test with fasting glucose and fructosamine concentrations determined at 36-38 weeks. Umbilical cord blood was taken for insulin, C peptide, fructosamine, SHBG, sex hormone, and insulin-like growth factor I (IGF-I) measurements, and neonatal anthropometry was measured 24 h after delivery. Babies from pregnancies complicated by diabetes were heavier, fatter, hyperinsulinemic (90.4 vs. 130.6 pmol/L, respectively; P < 0.01), with similar SHBG (44.0 +/- 6.5 vs. 44.2 +/- 12.0) and sex hormone levels and higher IGF-I concentrations (57.1 +/- 24.2 vs. 70.1 +/- 37.1; P < 0.05). There were no ethnic differences in cord SHBG, sex hormones, or IGF-I. SHBG correlated negatively with cord insulin concentrations [males, -0.31 (P < 0.01); females, -0.35 (P < 0.001)], birth weight [males, -0.25 (P < 0.05); females, -0.36 (P < 0.001)] and other measures of neonatal size. In both normal pregnancies and those complicated by diabetes, cord IGF-I correlated with cord C peptide levels [0.32 (0.32 (P < 0.001) and 0.42 (P < 0.05), respectively] and neonatal size, but only in normal babies was there a correlation between IGF-I and insulin [0.43 (P < 0.001) and 0.10] or SHBG [-0.28 (P < 0.01) and -0.01]. These data confirm that relationships between insulin concentration and SHBG are present at birth and are likely to be physiological.

Adult↗

Overnight secretion pattern of growth hormone, sex hormone binding globulin, insulin-like growth factor-1 and its binding protein in obese and non-obese women with polycystic ovarian disease.

The pathophysiological mechanism underlying polycystic ovarian disease (PCOD) is different in obese and lean women. In obese patients the basic disorder is insulin resistance and hyperinsulinemia. In non-obese women the dominant derangement is a relative excess of luteinizing hormone (LH) and growth hormone (GH) production. The levels of GH, LH, sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP-1) were significantly lower and insulin levels considerably higher in obese PCOD women as compared to their non-obese counterparts. There was, however, no difference in the mean IGF-1 levels found in these two groups. The present study was designed to investigate whether, in addition to the mean levels, the overnight pattern of GH, IGF-1, IGFBP-1 and SHBG differed in obese women with polycystic ovaries as compared to that observed in the non-obese PCOD patients. Eight women with PCOD diagnosed by clinical, sonographic and hormonal means were studied. Four had basal body mass index exceeding 27. Blood samples were collected every 20 min over a period of 8 h, starting at 23:00 h. Twenty-four samples were collected from each patient and examined in one batch for GH, IGF-1, IGFBP-1, SHBG and insulin. The secretion patterns of the above substances during the late night (23:00-03:00 h) and early morning (03:00-07:00 h) hours were examined and compared in obese and non-obese PCOD women. Neither GH nor IGF-1 showed a distinct overnight secretion pattern. The overnight secretion patterns of IGFBP-1 and SHBG were similar in obese and non-obese women--the former showing a constant rising during the night and the latter exhibiting a converse trend. The integrated insulin levels were much higher during the late night as compared to early morning hours in all patients. It is proposed that the specific secretion pattern of IGFBP-1 is not directly dependent on body fat mass but is regulated by insulin in both obese and non-obese patients.

Adult↗

Is there a "bladder sex"? The relation of different sex hormones and sex hormone receptors in bladder in childhood.

The aim of this study was to review the classical concept of bladder physiology in regard to sex hormone effects and to focus on a new concept. Sex hormones affect bladder functions and the classical concept tries to explain these effects via alpha and beta adrenoreceptors. The effects of hormones had been investigated in this understanding. To obtain a biological response to steroids in target tissues, specific proteins--so-called receptors--are warranted. After the demonstration of the sex hormone receptors in bladder first in adults and in children urge questioning the effects of hormones in this regard. The hypothesis is based on the fact that, if a special receptor is present, the direct (via sex hormone receptors) effect is more likely to occur as an indirect effect (via alpha and beta adrenoreceptors). There is evidence that there is a sex difference and the sex receptors and hormones play an important role in some bladder disorders. Therefore we stress the importance of investigating especially the pediatric patients with bladder problems in regard to sex hormone receptors and hormonal status.

Child↗

Sex hormones and sex hormone binding globulin in males with compensated and decompensated cirrhosis of the liver.

The present work investigates the sex hormone profiles in 50 male patients with liver cirrhosis of different etiology according to the degree of liver dysfunction. The only hormonal impairment in well-compensated cirrhotics (group A) was an increase in mean serum concentrations of estrone, androstenedione, and sex hormone binding globulin. In decompensated cirrhotic patients with ascites (group B), low mean levels of total and free testosterone were found along with normal gonadotropins mean levels. Estrone and androstenedione levels were still elevated, whereas sex hormone binding globulin levels were not different from controls. In decompensated cirrhotics patients with encephalopathy (group C), total and free testosterone mean levels were lower than in group B, and LH mean levels were elevated; estrone levels were markedly high, but androstenedione levels were subnormal; sex hormone binding globulin concentrations were again not different from controls. The few patients with high prolactin levels belonged primarily to this group. Estradiol mean levels were not significantly elevated in any of the groups. It is concluded that the various hormonal patterns of gonadal failure and of the impairment of steroid metabolism and transport, observed in cirrhosis, can be attributed to the degree of liver dysfunction.

Adult↗

Elevated levels of sex hormones and sex hormone binding globulin in male patients with insulin dependent diabetes mellitus. Effect of improved blood glucose regulation.

In a prospective study we have measured serum levels of sex hormone-binding globulin (SHBG), androgens, oestrogens and gonadotropins in 20 male IDDM patients with the aim of evaluating the effect of improved glycaemic control on these levels and to compare the IDDM patients with an age- and weight-matched healthy non-diabetic control group. The patients were chosen from the male IDDM patients attending the outpatient clinic at the Department of Endocrinology, Odense University Hospital. Glycaemic control was optimized by a trained diabetologist according to the patients' measurements of home blood glucose concentrations and reported hypoglycaemic episodes during a three month period. Prior to regulation the patients, compared to healthy control subjects, had significantly higher serum levels of oestrone (0.29 +/- 0.02 vs 0.16 +/- 0.01 nmol/l (Mean +/- SEM), p < 0.01), 17 beta-oestradiol (0.12 +/- 0.01 vs 0.08 +/- 0.01 nmol/l, p < 0.01), dihydrotestosterone (4.20 +/- 0.18 vs 1.66 +/- 0.09 nmol/l, p < 0.01), total testosterone (20.7 +/- 0.9 vs 17.8 +/- 1.1 nmol/l, p < 0.05) and SHBG (42.3 +/- 2.9 vs 15.5 +/- 3.5 nmol/l, p < 0.05), while the calculated free-testosterone was lower (0.34 +/- 0.02 vs 0.40 +/- 0.02 nmol/l, p = 0.068). After regulation, the patients obtained significantly lower levels of glycosylated haemoglobin (10.4 +/- 0.3 vs 8.9 +/- 0.2%, p < 0.005) and serum fructosamine (1.50 +/- 0.05 vs 1.34 +/- 0.04 nmol/l, p < 0.005) on a higher 24 hour insulin dose (52.7 +/- 4.4 vs 59.2 +/- 4.6 IU/24 h, p < 0.005). Levels of free-testosterone (0.41 +/- 0.04 nmol/l), oestrone (0.33 +/- 0.03 nmol/l), oestradiol (0.14 +/- 0.01 nmol/l), delta 4-androstenedione (4.44 +/- 0.43 vs 3.85 +/- 0.42 nmol/l), and prolactin (249 +/- 24 vs 200 +/- 19 mIU/l) increased compared to values obtained before regulation (all p < 0.05). We conclude that SHBG, testosterone, dihydrotestosterone and oestrogen levels are increased in male IDDM patients. High SHBG levels tend to keep the free fractions of sex hormones within normal limits. During improvement of glycaemic control with insulin, levels of free-testosterone and its bioprecursors and metabolites rise. This may partly be due to the increased daily insulin dose and/or to the improvement in glycaemic control itself.

Adult↗

Serum lipoproteins, sex hormones and sex hormone binding globulin in middle-aged men of different physical fitness and risk of coronary heart disease.

Serum concentrations of lipoproteins, apolipoprotein A-I (Apo A-I), androgens, including biologically active free testosterone (free T), and sex hormone binding globulin (SHBG) and their associations were studied in 3 groups of men of different physical fitness and risk of CHD, consisting of male CHD patients, joggers and healthy controls. Of the 3 study groups, men with angiographically assessed CHD had the lowest HDL-C (P less than 0.002) and highest LDL-C and triglyceride (TG) levels (P = 0.05 and P less than 0.001) and lower 5 alpha-dihydrotestosterone (5 alpha-DHT) levels than joggers (P less than 0.02). Joggers had the highest serum high density lipoprotein cholesterol (HDL-C), Apo A-I and SHBG levels and lowest serum low density lipoprotein cholesterol (LDL-C) compared to the other groups (P less than 0.01). In correlation analysis 5 alpha-DHT was the most significant positive determinant of HDL-C and Apo A-I levels in CHD patients (r = 0.56 and r = 0.55, respectively, P less than 0.05). Moreover, SHBG was significantly positively correlated to both HDL-C and Apo A-I levels in patients, in the whole study group and in healthy men separately (r = 0.37-0.52, P less than 0.01). These significant correlations were also confirmed when age variation and differences in body mass index and smoking were controlled in multivariate analysis and in addition, in multivariate analysis both serum free and total testosterone were inversely related to serum triglyceride (TG) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women.

Sex steroid hormones in both males and females have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Evidence also suggests a direct relationship between sex hormones and risk factors for cardiovascular disease. In the present review article, we will discuss recent studies that have examined the complex interrelationships between sex hormones, SHBG, obesity and risk factors for cardiovascular disease. Male obesity and excess abdominal adipose tissue accumulation is associated with reductions in gonadal androgen and low adrenal C19 steroid concentrations. Reduced C19 steroids are also related to an altered metabolic risk factor profile including glucose intolerance and an atherogenic dyslipidemic state. However, the concomitant visceral obese state appears as a major correlate in these associations. In women, menopause-induced estrogen deficiency and increased androgenicity are associated with increased abdominal obesity and with the concomitant alterations in the metabolic risk profile. The accelerated accretion of adipose tissue in the intra-abdominal region coincident with the onset of menopause may explain part of the increased risk of cardiovascular disease in postmenopausal women. In both men and women, plasma levels of sex hormone-binding globulin are strong correlates of obesity and risk factors for cardiovascular disease, and more importantly, the relationships between low SHBG and altered plasma lipid levels appear to be independent from the concomitant increased levels of visceral adipose tissue. SHBG concentration may, therefore, represent the most important and reliable marker of the sex hormone profile in the examination of the complex interrelation of sex steroid hormones, obesity, and cardiovascular disease risk.

Adipose Tissue↗

Sex differences in verbal and spatial ability reconsidered in relation to body size, lung volume, and sex hormones.

Sex differences in verbal and nonverbal abilities were reconsidered in relation to bodily measures and sex hormones in Turkish university students. Perceptual-verbal ability was evaluated using As Test. To assess the nonverbal abilities, the mental rotation test and Cattell's Culture Fair Intelligence Test were used. As expected, the 53 women performed better than men on the As Test; 79 men had a higher mean than the 53 women on the mental rotation task; there was no sex difference on Cattell's IQ Test. Cattell IQs correlated only with tidal volume of lungs. Scores on the As Test did not show significant correlations with body size and lung capacities. Mental rotation was significantly correlated with height, weight, and lung volume. With covariates of height, weight, and vital capacity, sex differences in mental rotation completely disappeared, but the difference on the As Test increased while Cattell IQ remained sex-neutral. With testosterone as covariate, the sex difference on the As test increased but on the mental rotation task disappeared; Cattell IQ was sex-neutral. With covariates of estradiol and progesterone, sex differences on the As test disappeared; mental rotation scores and Cattell IQ were not influenced. Under a combined covariation of height, weight, and testosterone, sex differences in mental rotation reversed, women scoring better than men; after adding estradiol or progesterone instead of testosterone to this model, sex differences on mental rotation completely disappeared, but verbal ability and Cattell IQ were not changed. These results suggest that Cattell's Culture Fair Intelligence Test is unique in resistance to sex differences; perceptual-verbal ability was the most sex-specific mental trait but with dependence on estradiol; mental rotation, on the contrary, was least sex-specific, depending on body size, lung volume, sex hormones, and their combined actions, which explains women's better performance.

Adolescent↗

Relationship between insulin resistance, sex hormones and sex hormone-binding globulin in the serum lipid and lipoprotein profiles of Japanese postmenopausal women.

The purpose of the present study was to investigate the relationship between insulin resistance, sex hormones and sex hormone-binding globulin (SHBG) in regard to the serum lipid and lipoprotein profiles of 82 Japanese postmenopausal women. A multiple regression analysis for lipids, lipoproteins, and apoproteins as dependent variables was performed. All regression models included the following variables as potential independent variables; BMI, percentage of body fat, waist-hip ratio, free testosterone (Free T) and SHBG. In addition, model A included insulin resistance evaluated by HOMA-R and model B included fasting insulin (FIRI). In model A, both Free T and HOMA-R were independent predictors of total-C (TC)/high-density lipoprotein-C (HDL-C) and low-density lipoprotein-C (LDL-C)/HDL-C. The BMI was independently associated with HDL-C. The Free T was a single independent predictor of TC and LDL-C. Both BMI and HOMA-R were independent predictors of triglyceride (TG). In addition, SHBG was also independently associated with apoprotein B (Apo B) and Apo B/Apo AI. In model B, FIRI was an independent predictor of lipid metabolism with similar results to those observed in model A. These results suggest that the lipid characteristics in postmenopausal women might be associated with insulin resistance and/or hyperinsulinemia, and relative hyperandrogenicity which thus induces an increase in the amount of Free T and a decrease in the SHBG within physiological ranges.

Adult↗

[Periodontal tissues and sex hormones. Effects of sex hormones on metabolism of fibroblasts derived from periodontal ligament].

Sex hormones are closely related to the onset and progression of periodontal disease. The purpose of this study was to evaluate the effects of sex hormones on the metabolism of human periodontal ligament cells. Human periodontal ligament cells and gingival fibroblasts were prepared from 7 donors with normal gingiva. 17 beta-estradiol and progesterone were purchased from Sigma Chemical Company. The effects of sex hormones on cell morphology, alkaline phosphatase activity, cell proliferation, DNA synthesis, collagen synthesis and non-collagenous protein synthesis were investigated. The results were as follows: 1. Periodontal ligament cells showed osteoinductive-like cells in the cell morphology and alkaline phosphatase activity. 2. DNA synthesis was stimulated by 17 beta-estradiol and progesterone in the presence of 5% fetal calf serum. 3. Collagen synthesis was inhibited by 17 beta-estradiol and progesterone, while non-collagenous protein synthesis was inhibited by 17 beta-estradiol and low concentrations of progesterone. 4. The addition of serum into culture medium was necessary to induce the basic metabolism of human periodontal ligament cells. It was demonstrated that sex hormones are closely related to the metabolism of human periodontal ligament cells.

Alkaline Phosphatase↗

Sex hormones and sex hormone-binding globulin in males with chronic viral hepatitis during recombinant interferon-alpha 2b therapy.

The effect of long-term treatment with recombinant interferon-alpha 2b (IFN-alpha 2b) on luteinizing hormone (LH), testosterone, free testosterone, and sex hormone-binding globulin (SHBG) was evaluated in 7 male patients suffering from chronic viral hepatitis. The drug was given three times a week for 6 months in a single standard dose of 3 x 10(6) units. Hormone evaluations were performed in basal conditions and every 2 months for 12 months. Serum testosterone values decreased after IFN treatment, reaching the lowest levels at the 6th month. However, testosterone values did not fall below the normal range. Serum SHBG concentrations, which were above the normal range in basal conditions, also decreased after IFN. Serum-free testosterone and LH concentrations did not change during IFN therapy. IFN-alpha 2b at the dose and schedule employed was not responsible for any measurable imbalance in male sex hormones.

Adult↗

Analysis of thymocyte subpopulations following treatment with sex hormones.

Sex steroids were found to affect both murine and avian immune systems. Female and male (NZB X NZW)F1 mice were castrated at 2 weeks of age and given Silastic implants containing either dihydrotestosterone or estradiol. Four weeks following treatment, the thymuses were studied for cell cycle kinetics and for the presence of various cell surface antigens using fluorescein-conjugated antisera and flow cytometric techniques. Estradiol therapy resulted in an increase in mature thymocytes, that is, thymocytes that had decreased peanut agglutinin receptors and decreased Thy 1 antigens on their surfaces. Additional studies with anti-Lyt 1 and 2 indicated that these mature thymocytes were of the "helper" rather than the "suppressor" phenotype. Estradiol therapy resulted in an increase in the percentages of proliferating cells in the spleen and a decrease in the percentages of proliferating cells in the thymus. In contrast, in the avian system, estradiol had little effect on proliferation in immunological organs. Dihydrotestosterone was a potent inhibitor of proliferation in the avian bursa. These results indicate that sex hormones have specific effects on different immune cell subpopulations. In the murine system the male is the heterogametic sex but in the avian system the female is the heterogametic sex. Based upon the present and previous studies, we suggest that the primary modulating hormone for immunological sex effects in the mammal is estrogen, whereas in the bird it is androgen.

Animals↗

The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.

The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively associated with albumin-bound testosterone, DHEA, and DHEAS. An association was found between alcohol intake and DHEA (r = 0.15; P = 0.0001), cortisol (r = 0.10; P = 0.0007), and 3-alpha-androstanediol-glucuronide (r = 0.08; P = 0.0004). Cortisol was the only hormone that was associated with carbohydrate intake (r = -0.09; P = 0.002). The only hormones associated with dietary lipids were DHT (for vegetable fat, r = 0.07; P = 0.02), cortisol (for total fat, r = 0.08; P = 0.007), and SHBG (for animal fat, r = -0.06; P = 0.05). In addition, SHBG was positively associated with dietary (r = 0.07; P = 0.008) and crude (r = 0.08; P = 0.007) fiber. These data suggest that serum adrenal steroid and sex hormone concentrations in middle-aged men are more influenced by cigarette smoking, age, and obesity than by dietary intake; however, serum adrenal steroids were influenced by alcohol intake.

Adrenal Glands↗