High dose testosterone therapy for reduction of final height in constitutionally tall boys: does it influence testicular function in adulthood?

OBJECTIVE We have studied the effect of treatment with high doses of androgens during puberty on testicular function In adult men with constitutionally tall stature, taking Into account confounding factors interfering with sperm quality, since existing published data do not include whether testicular function is impaired by such treatment. DESIGN Historical cohort study. PATIENTS Forty-three previously androgen treated tall men (cases) and 30 non-treated tall men (controls). MEASUREMENTS Physical examination, semen analysis and plasma levels of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and Inhlbin. RESULTS Sperm quality and testis volume were comparable between cases and controls. Mean sperm concentration was 66.4 ± 10⁶/ml in cases and 66.2 ± 10⁶/ml in controls. A left-sided varicocele was found In 45% of the cases and 37% of the controls. In cases we observed a significant effect of the age at start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%, P= 0.048). In addition, testicular size at start of therapy had a significant effect on sperm concentration (regr. coeff. (SE): 5.57 (1.54) ± 10⁶/ml, P= 0.0012) and on total sperm count (regr. coeff. (SE): 43.1 (7.73) ± 10⁶, P= 0.0001). Plasma levels of T, SHBG and Inhibin were not statistically different between the groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2) vs 2.1 (0-8) IU/I, P= 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9) vs 3.1 (1.4) IU/I, P= 0.019). We found a significant effect of age at start of therapy on plasma FSH level In the treated men (regr. coeff. (SE): ?0.73 (0.18) IU/I, P= 0.0003). CONCLUSIONS Treatment with high doses of androgens for reduction of final height in constitutionally tall stature has no long-term side-effect on sperm quality, testicular volume or plasma testosterone levels. However, treated men had significantly higher plasma levels of FSH compared with controls. The meaning of this difference remains to be established. Varicocele was present in 42% of the adult tall men.     

Increased serum inhibin B levels after varicocele treatment

OBJECTIVE: Inhibin B is secreted by Sertoli cells in response to FSH and is the major feedback regulator of FSH secretion in man. The serum inhibin B level has emerged as a good marker of spermatogenesis and Sertoli cell function. Varicocele has been associated with infertility and disturbed spermatogenesis. We have studied the effect of varicocele treatment on serum inhibin B levels, with the aim of investigating the effect on spermatogenesis and the involvement of the Sertoli cell in varicocele pathophysiology. DESIGN AND PATIENTS: In a pre-post test design, the effect of varicocele surgery on inhibin B levels was studied in 30 infertile men. MEASUREMENTS: Endocrinology (inhibin B, FSH, LH, SHBG and testosterone) and semen analysis (sperm concentration, motility and morphology). RESULTS: In men receiving varicocele treatment, a significant increase in serum inhibin B levels was observed from 133.9 +/- 13.4 pretreatment to 167.8 +/- 16.1 ng/l after treatment (mean +/- SEM, P < 0.0001). No significant changes were observed in serum levels of FSH, LH and testosterone. The serum SHBG level decreased from 32.9 +/- 3.5 to 28.6 +/- 3.4 nmol/l (mean +/- SEM, P = 0.04) and the free androgen index was significantly increased from 66 +/- 5.9 pretreatment to 85 +/- 6.8 after treatment (P = 0.02, mean +/- SEM). Semen analysis showed a significant improvement in sperm concentration, from 6.5 +/- 1.9 pretreatment to 19.3 +/- 4.9 x 106/ml after treatment (P = 0.003, mean +/- SEM), and in sperm motility from the baseline level of 17 +/- 3 to 32 +/- 4% after treatment (P = 0.001, mean +/- SEM). CONCLUSIONS: Varicocele treatment can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function. This finding suggests that the pathophysiology of varicocele involves impairment of Sertoli cell function or a different distribution of germ cell stages.     

Lack of evidence of a genetic origin in the impaired spermatogenesis of a patient cohort with low-grade varicocele

Varicocele is the most common clinical finding in infertile men but controversy continues to surround the utility of its treatment. An increased response of FSH to gonadotrophin-releasing hormone testing has been described in patients with varicocele, while the co-influence of Yq chromosome microdeletions in the infertility associated to this pathology is still under investigation. We studied 30 patients with first- and second-grade varicocele, 15 idiopathic oligozoospermic men and 21 age-matched healthy controls. All subjects underwent testicular Doppler ultrasonography, semen analysis, gonadotrophin-releasing hormone testing and baseline blood sampling for total and free testosterone, PRL, 17beta-estradiol, SHBG evaluation and Yq chromosome analysis. Apart from FSH, no difference in baseline hormonal levels was found between the groups. The patients with varicocele showed both an increased basal (p=0.007) and GnRH-induced FSH response (peak and AUC) (p=0.004) in comparison with the controls, while the idiopathic oligozoospermic men had only higher GnRH-induced FSH AUC (p=0.04). In the varicocele group, FSH peaks after GnRH testing correlated positively with the grade of disease (r=0.42, p=0.02) and negatively with sperm count (r=-0.50, p=0.005) and bilateral testis volume (r=-0.52, p=0.005). Sperm count and sperm motility were similarly significantly reduced both in patients with varicocele and in patients with idiopathic oligozoospermia in comparison with healthy controls. Yq chromosome analysis by sequence-tagged site PCR revealed no microdeletion in the AZF regions in any subject studied. Given the quite small number of subjects studied, our overall findings can only prompt us to suggest a possible causal role of varicocele in the impairment of spermatogenesis in our patients. Furthermore, although a genetic co-influence (i.e. Yq microdeletions) does not seem to be involved in the pathogenesis of infertility in men with varicocele and mild to moderate oligozoospermia, genetic screening seems to be advisable, especially in those patients who present a severe impairment of sperm count, as has been suggested by recent literature data.     

Gonadal hormones and gonadal function in type 2 diabetes model OLETF (Otsuka Long Evans Tokushima Fatty) rats

Gonadal functions, with special reference to blood levels of sex-related markers such as 17beta-estradiol (E2), free testosterone (free Te) and lutenizing hormone (LH), were examined in male OLETF (Otsuka Long Evans Tokushima Fatty) diabetic rats, a model of human type 2 diabetes mellitus. Male rats of the OLETF strain and male rats of the LETO strain, which act as a control of OLETF, both supplied by Otsuka Pharmaceutical Co., Ltd. (Tokushima, Japan), were periodically examined for blood levels of E2, free Te and LH at the age of 4, 5, 32, 40 and 64 weeks. The weight of the testis, the number of sperm contained within and histological findings of the testis were comparatively studied in both strains. Glucose and insulin (IRI) at fasting were examined to evaluate the homeostasis model assessment (HOMA) index. In order to investigate any sex hormone imbalance, sex hormone-binding globulin (SHBG) was measured by a dextran- charcoal assay. All of the OLETF rats became diabetic at the age of 32 weeks. There were no significant differences between OLETF and LETO rats regarding free Te, E2, LH or SHBG during the observation period from 4 to 64 weeks. Testis weight was significantly decreased in OLETF rats at 32 and 64 weeks and sperm counts at 64 weeks of age were also significantly decreased. Histologically, there was seminiferous tubule atrophy in the OLETF rats at 64 weeks of age. A significant negative correlation between testis weight and fasting blood glucose, as well as HOMA index, was observed in OLETF rats. In male diabetic OLETF rats, with a variety of hypogonadisms such as atrophy of the testis and low sperm count, the serum levels of E2, free Te, LH and SHBG were normally preserved.     

Relationship of serum inhibin levels to serum follicle stimulating hormone and sperm production in normal men and men with varicoceles.

The purpose of this study was to examine the relationships between serum inhibin levels as measured by RIA and serum FSH and sperm concentration. Three groups of men were used for this study: group I, normal fertile men (n = 67); group II, fertile men with a varicocele (n = 57); and group III, infertile men with a varicocele (n = 21). There were no differences in mean serum inhibin levels between the three groups. The two groups of men with varicoceles exhibited higher serum FSH levels and FSH responses to GnRH than the normal men. Sperm counts in both groups II and III were significantly lower than group I. In the normal men there was an inverse correlation between baseline serum inhibin and serum FSH levels and GnRH stimulated FSH levels, r = -0.415 and 0.422, P less than 0.005, respectively. Furthermore, the normal men exhibited a positive correlation between serum inhibin measurements and sperm concentration and testicular volume, r = 0.35 and 0.26, P less than 0.01 and less than 0.05, respectively. In neither group of men with a varicocele were these relationships found. These data demonstrate that serum inhibin does correlate with FSH in a negative fashion, when the reproductive system is normal, as would be expected for a negative feedback factor. Finally, the relationship of serum inhibin levels to testicular size and sperm count in the normal men suggests that serum inhibin levels reflect to some extent the integrity of seminiferous tubule function.     

精索静脉曲张患者血清生殖激素、精子形态、精子活率的变化

目的探讨精索静脉曲张（VC）对生殖激素及精子形态、精子活率的影响。方法检测81例VC所致男性不育患者和18例健康生育男性精液及血清标本,其中不育患者按VC临床分度分为Ⅰ°、Ⅱ°和Ⅲ°组,用放射免疫法测定血清催乳素（PRL）、卵泡刺激素（FSH）、黄体生成素（LH）、睾酮（T）、雌二醇（E2）水平;采用计算机辅助精液分析仪测定精子活率。结果Ⅱ°和Ⅲ°组FSH、LH低于对照组（P〈0．05）;Ⅰ°、Ⅱ°和Ⅲ°组的T、PRL和E2与对照组相比差异无统计学意义（P〉0．05）;Ⅱ°和Ⅲ°组正常形态精子百分率低于对照组（P〈0．05）;VC各组精子活率均低于对照组（P〈0．05）,且Ⅲ。组精子活率低于Ⅰ°和Ⅱ°组（P〈0．05）。结论VC可引起血清生殖激素FSH、LH变化,但VC临床分度对血清生殖激素水平的影响关系不明显。VC能够导致正常形态精子百分率和精子活率下降,VC程度越重,对精液正常形态精子率与活率的影响程度越大。     

5'-Nucleotidase activity is decreased in seminal plasma and spermatozoa from varicocele patients

5'-Nucleotidase is involved in sperm capacitation via the cAMP-adenosine pathway and in sperm motility via direct adenosine production from AMP. Since these functions are reduced in varicocele, the aim of this study was to investigate whether the enzyme levels were altered in sperm from varicocele patients. The mean (SD) international units (IU) of 5'-nucleotidase activity in seminal plasma from 35 varicocele III patients was 0.16(0.09) IU ml(-1) vs 0.35(0.13) IU ml(-1) in 53 controls, this decrease being statistically significant at p < or = 0.001. A significant decrease in activity, expressed as international units per mg of protein concentration in spermatozoa homogenates, was also observed with spermatozoa: 0.0018(0.0017) IU mg(-1) in varicocele III vs 0.0081(0.0060) IU mg(-1) in controls, at p < or = 0.001. Compared to controls, the activity decrease observed both in spermatozoa and seminal plasma from 45 men with varicocele I was not statistically significant at p < or = 0.05. To determine the diagnostic value of 5'-nucleotidase in assessing sperm fertility in varicocele III, we used the likelihood ratios method and best cut-offs were identified in receiver operating characteristic curves. With a prevalence of 36%, the post-test probability of infertility was 91% in spermatozoa and 78% in seminal plasma. The cut-off values of 5'-nucleotidase activity discriminating for fertile/unfertile semen were 0.2 IU ml(-1) in seminal plasma and 0.003 IU mg(-1) of protein in spermatozoa. Overall, determination of 5'-nucleotidase activity, especially in spermatozoa, can be useful to characterize different varicocele degrees as well as the sperm fertility potential.     

High endogenous melatonin concentrations enhance sperm quality and short-term in vitro exposure to melatonin improves aspects of sperm motility

Although human seminal fluid contains melatonin and spermatozoa reportedly possess membrane melatonin receptors, there are no experimental studies that have ascertained the relationship between melatonin and male infertility. This study evaluated whether urinary 6-sulfatoxymelatonin and urinary total antioxidant capacity correlate with different seminal parameters including sperm concentration, motility and morphology. Also, the in vitro effects of melatonin on human sperm motility were investigated. Semen samples from 52 men who were counselled for infertility were obtained. Sperm concentration was determined using the haemocytometer method, motility kinematic parameters were assessed using a computer-aided semen analysis system, while morphology and vitality were evaluated after Diff-Quick and Eosin-Nigrosin vital staining, respectively. For the quantification of urinary 6-sulfatoxymelatonin, a commercial ELISA kit was used, and urinary total antioxidant capacity was evaluated by means of a colorimetric assay kit. For the in vitro effects of melatonin, samples were incubated for 30min in the presence or absence of 1mm melatonin. Both urinary 6-sulfatoxymelatonin and total antioxidant capacity levels positively correlated with sperm concentration, motility and morphology, as well as negatively correlated with the number of round cells. Additionally, 30-min exposure of sperm to 1mm melatonin improved the percentage of motile and progressively motile cells and decreased the number of static cells, thereby promoting the proportion of rapid cells. Therefore, melatonin improves semen quality, which is important because melatonin supplementation may be potentially used to obtain a successful assisted reproductive technique outcome.     

Development of l-CDB-4022 as a nonsteroidal male oral contraceptive: induction and recovery from severe oligospermia in the adult male cynomolgus monkey (Macaca fascicularis)

The present study was undertaken to examine the antispermatogenic effect of l-CDB-4022 in the adult male cynomolgus monkey. Monkeys (four per group) were dosed via nasogastric tube for 7 d with l-CDB-4022 at 12.5 mg/kg.d or vehicle (d 0=first day of dosing). Plasma levels of l-CDB-4022 and its deesterified metabolite were nondetectable prior to treatment and in all vehicle-treated monkeys. Peak levels of l-CDB-4022 and its metabolite were observed at 4 h after dosing with steady-state levels apparent around d 4. Sperm concentration and total sperm per ejaculate were decreased to levels below 1x10(6) sperm/ml or sperm/ejaculate in l-CDB-4022-treated monkeys by d 17 and remained suppressed through wk 6. Sperm motility also declined to 0% for 6 wk. Testicular volume was reduced in l-CDB-4022-treated monkeys through d 21. The left testis and epididymis were removed from all monkeys on d 24. At this time, the most mature germ cells in the seminiferous tubules of testes from l-CDB-4022-treated monkeys were either spermatocytes or round spermatids. Immature germ cells, but not mature sperm, were found in the efferent ducts and collapsed epididymal lumen of l-CDB-4022-treated monkeys. A steady recovery in sperm motility, concentration, and total sperm per ejaculate was observed in l-CDB-4022-treated monkeys such that these parameters were not different from those of vehicle-treated monkeys by wk 16. Volume of the remaining testis increased in vehicle- and l-CDB-4022-treated monkeys after hemicastration; however, the increase in l-CDB-4022-treated monkeys was delayed compared with that observed in the vehicle-treated monkeys. The morphology of the remaining testis and epididymis, which were removed on wk 17, was normal. Serum inhibin B levels were increased in l-CDB-4022-treated monkeys during the dosing interval; thereafter serum inhibin B levels declined such that there was no difference between the groups by wk 3. l-CDB-4022 treatment did not affect circulating levels of testosterone, LH, FSH, or estradiol. In conclusion, these data indicate that in the cynomolgus monkey, a representative higher primate, l-CDB-4022 exerts a selective antispermatogenic action, which was reversible under the conditions of this study and thus has potential as a nonhormonal oral male contraceptive.     

Interstrain differences in angiotensin I-converting enzyme mRNA and activity levels. Comparison between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.

Plasma angiotensin I-converting enzyme (ACE) levels are different between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKYHD) rat. This interstrain variability in plasma ACE levels is independent of blood pressure and is genetically linked to the ACE gene. The present study explored the hypothesis of an interstrain variability of tissue ACE activity and ACE gene expression levels. Tissue ACE levels were studied by enzymic activity measurement in the membrane fraction, and ACE mRNA levels were quantified by solution hybridization-ribonuclease protection assay. In lung, heart, kidney, and duodenum, membrane-bound ACE activity and ACE mRNA amount were significantly higher in WKYHD rats compared with SHRSPHD rats. No difference was observed in the testis where a specific isoform of the enzyme is produced. Our results suggest that in addition to determine differential plasma ACE levels between the WKYHD and SHRSPHD strains, the interstrain genetic variability also determines differential ACE mRNA and membrane-bound enzyme levels in somatic tissues. This likely reflects a difference in the ACE gene expression due to genetically determined regulatory mechanisms operative in all somatic tissues.     

精液白细胞与精子DNA完整性、精子参数的关系

目的探讨精液白细胞与精子DNA完整性、精子参数的关系。方法分析156例男性不育患者精液标本,采用联苯胺染色法检测精液白细胞,吖啶橙荧光染色检测精子DNA完整性。采用计算机自动分析精子密度与活力,采用精子形态检测系统下人工修正方法进行精子形态分析。结果精液白细胞异常者精子密度、精子活力降低（P〈0.05）,精子DNA完整率异常率增高（P〈0.05）。精子DNA完整率异常者精子密度、活力降低（P〈0.05）,精子形态无明显变化（P〉0.05）。结论精液白细胞可直接影响精子参数、精子DNA完整率,又可能通过精子DNA完整率异常影响精子参数。     

Dietary lipids: an additional regulator of plasma levels of sex hormone binding globulin

The effect of dietary lipid consumption on plasma levels of sex-hormone binding globulin (SHBG), free testosterone and cholesterol was studied in 6 normal men. After consuming a diet with a high fat content (greater than 100 g fat/day) for two weeks, the mean plasma cholesterol level increased (p less than 0.02) while the mean SHBG level decreased (p less than 0.02). Changing the diet from one with a high fat to low fat content (less than 20 g fat/day) for a further two week period resulted in a significant reduction in mean plasma cholesterol level (p less than 0.001) while the mean SHBG level increased (p less than 0.01). The increase in plasma SHBG was associated with a significant decrease in the free testosterone fraction and free testosterone concentration. No significant changes were detected in plasma samples obtained from the same men during a control period. The results from this study demonstrate that dietary lipid intake is an additional factor involved in the regulation of plasma levels of SHBG.     

Antisperm antibodies in the polyglandular autoimmune (PGA) syndrome type I: response to cyclical steroid therapy

OBJECTIVE: To determine if cyclical intermediate dose steroid therapy could improve semen parameters in an infertile man with sperm autoimmunity associated with the polyglandular autoimmune (PGA) syndrome. DESIGN: Sperm agglutination studies performed before, during and after three courses of cyclical intermediate dose prednisolone therapy. PATIENT: A twenty-six-year old man with polyglandular autoimmune syndrome, consisting of Addison's disease, hypoparathyroidism, chronic mucocutaneous candidiasis and alopecia totalis, presented with infertility. He had normal endocrine testicular function but severe exocrine failure evidenced by a low sperm count (4.5 x 10(6)/ml), zero motility and universal sperm agglutination. MEASUREMENTS: Sperm agglutination tests. RESULTS: At presentation the gelatin agglutination test (GAT) was strongly positive in serum (1/1204) and seminal plasma (1/64) as was the tray agglutination test (TAT) (1/32). The patient's wife had a regular menstrual cycle with normal luteal phase progesterone levels. Following three courses of cyclical prednisolone (20 mg twice daily on days 1-10 of wife's cycle, and 5 mg on days 11 and 12), sperm quantity and motility improved considerably (12 x 10(6)/ml, 40% respectively) and sperm agglutination tests became negative. After a fourth course of therapy the patient's wife became pregnant. Three months post-treatment sperm motility was very low again and agglutinating activity in serum and seminal plasma increased. CONCLUSIONS: This is the first case of male infertility due to sperm autoimmunity in association with the PGA syndrome type 1. The immunosuppressive action of cyclical intermediate dose steroid therapy led to a significant quantitative and qualitative improvement in semen parameters.     

Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes

OBJECTIVE: To study the risk factors for HIV-1 in semen according to the localization of HIV-1 in sperm cell fractions and to assess the efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. METHODS: Ninety-four HIV-infected patients provided 281 paired blood and semen samples. Sperm cell separation was performed using two successive methods. HIV-1 RNA was quantified in blood and seminal plasma. HIV-1 RNA and DNA were detected in cell fractions. RESULTS: HIV-1 RNA was found in 14% of seminal plasma samples and up to 8.7% of native semen cells were positive for HIV-1 RNA and DNA. Ten seminal plasma samples had detectable RNA although blood viral load was undetectable. Antiretroviral treatment reduced the likelihood of RNA detection in seminal plasma. For semen with polynuclear cells and HIV-1 RNA in seminal plasma, the likelihood of detecting HIV-1 genomes in semen cells was increased fourfold and sixfold, respectively. In 25% of patients, HIV-1 excretion was intermittent. In the group of patients with systematic negative seminal plasma, HIV-1 genomes were detected in up to 10% of sperm cell samples. Our method of sperm processing always enabled us to obtain spermatozoa without detectable HIV-1 genomes. CONCLUSIONS: Polynuclear cells in semen are a risk factor for seminal HIV-1 excretion. Blood viral load was the only predictive factor for the intermittence of HIV-1 excretion in semen over time. Sperm processing using two successive methods was effective in obtaining spermatozoa without detectable HIV-1 genomes regardless of the viral load level in native semen.     

Constancy in Human Sperm DNA Content

The frequency distribution of DNA content of human sperm was measured in an automated flow microfluorometer. The flow method measures the DNA content by quantifying the amount of fluorescence emitted by the fluorescent Feulgen stained DNA of single sperm cells suspended in microdroplets. The variability in the mean value for the haploid amount of DNA in sperm from 15 randomly chosen donors was less than 1%. Statistical tests on the observed frequency distribution data indicated that each sperm population probably consists of two homogenous components present in almost equal proportions but differing in mean DNA content. The difference in their modal values for DNA is within the range of known values of DNA difference between the two sex chromosomes.Sperm of donors segregating balanced translocations, when compared to the random samples as a class, showed greater variability in the mean DNA content.     

Application of a Time-Resolved Fluoroimmunoassay for the Analysis of Normal Prion Protein in Human Blood and Its Components

BACKGROUND AND OBJECTIVES: To quantify the cellular isoform of prion protein (PrP(c)) in human blood using a new time-resolved dissociation-enhanced fluoroimmunoassay (DELFIA). MATERIALS AND METHODS: The DELFIA was optimised for human blood samples and applied to isolated cell and plasma fractions from blood donations. The physicochemical properties of PrP(c) were analysed. RESULTS: 26. 5% of blood PrP(c) was associated with the platelet fraction, 0.8% with polymorphonuclear leucocytes, 2.4% with mononuclear leucocytes, 1.8% with red cells and 68.5% with plasma (mean values from 4 processed donations). CONCLUSION: The majority of blood PrP(c) is found in the platelet and plasma compartments.     

Effects of surgery, medical therapy and combined therapeutical approach on spermatogenesis in patients suffering from varicocele: a prospective and comparative analysis

The definite mechanisms through which varicocele affects spermatogenesis are still not completely understood, and consequently the exact role of the various approaches available for its treatment is still under debate. In this study a comparison of medical treatment, surgery and combined approach is reported. MATERIAL AND METHODS. The study was conducted as a prospective evaluation of 189 patients suffering from varicocele and oligoasthenospermia. Patients were randomized in three groups on the basis of the different therapeutic approach: group A, treated only with varicocelectomy; group B, treated with varicocelectomy associated with hormonal therapy; group C, treated only with hormonal therapy. Randomization criteria were based on patient's preference. Spermiogram tests were carried out at baseline and after 3, 6 and 12 months from therapy. RESULTS. Our results show that patients undergoing a combined therapeutical approach (surgery associated with hormonal therapy) and medical therapy alone achieve a greater improvement of seminal parameters than patients treated by surgery only. CONCLUSION. Data reported in this study are in accordance with Literature review. Furthermore, the association between varicocelectomy and early use of hormonal therapy seems to improve testis functional rehabilitation with a early evidence of sperm parameters improvement. In the light of these results of ours, we should conclude that surgical treatment is not effective for the spermatogenesis improvement.     

Effect of a six-week national cholesterol education program step 1 diet on plasma sex hormone-binding globulin levels in overweight premenopausal women

Background: Low circulating sex hormone-binding globulin (SHBG) concentrations have been associated with the presence of several features of the metabolic syndrome in both men and women. Nutritional factors including dietary lipids and fibers in particular have been suggested to modulate plasma SHBG levels. Methods: The primary objective of the present study was to investigate the effect of an oat bran-rich supplement in conjunction with the National Cholesterol Education Program (NCEP) Step 1 diet (< 30% of total energy from fat, < 10% of energy from saturated fat, and < 300 mg cholesterol per day) on plasma SHBG levels in 35 overweight premenopausal women. Subjects (age 38.6 +/- 7.4 years) had normal menstrual cycles and were tested in the midluteal phase. Since no effect of the oat bran supplement was observed on plasma SHBG levels, data were analyzed according to the 6-week NCEP Step 1 diet. Results: The NCEP Step 1 nutritional intervention caused a significant decrease in energy intake ( -11%, p < 0.05), percent fat intake (-10%, p < 0.005), as well as saturated (-20%, p < 0.005) and monounsaturated (-10%, p < 0.05) fatty acid intake. Body mass index (BMI) decreased slightly but significantly (from 29.2 +/- 4.5 to 28.8 +/- 4.3 kg/m(2), p < 0.005). Plasma SHBG levels increased significantly (from 70.6 +/- 17.7 to 79.9 +/- 15.3 pmol/L, p < 0.0005) following the 6-week NCEP Step 1 diet, whereas plasma insulin levels were not modified significantly. Significant correlations were observed between the change in plasma SHBG levels and baseline BMI (r = 0.36, p < 0.04), as well as baseline (r = -0.42, p < 0.05) and postintervention (r = -0.35, p < 0.05) HDL cholesterol levels. Conclusions: We observed that a 6-week NCEP Step 1 diet significantly increased plasma SHBG levels, despite the finding that fasting insulin was not modified. Further studies are needed to elucidate physiological mechanisms underlying a direct effect of dietary composition on SHBG production by the liver.     

DEMONSTRATION OF SEX HORMONE BINDING GLOBULIN IN HUMAN CEREBROSPINAL FLUID

This study demonstrates the existence of sex hormone binding globulin (SHBG) in human cerebrospinal fluid (CSF) by means of a highly sensitive radioligand saturation assay that has been recently described by us for measurement of SHBG in human plasma. The molecular similarity of this 5 alpha-dihydrotestosterone binding protein with plasma-SHBG was substantiated by a number of experiments in which the CSF-protein displayed the same properties as plasma-SHBG with respect to thermolability, affinity, specificity and sedimentation rate. SHBG levels in the CSF of normal women were found to be 0.139 +/- 0.04 nmol/l (mean +/- standard deviation), and in normal men to be 0.083 +/- 0.03 nmol/l respectively. CSF-SHBG in patients with a variety of neurological diseases associated with different degrees of a blood-CSF barrier disturbance, showed a good correlation with commonly determined parameters such as CSF-albumin and CSF-IgG that are known to be of plasma origin. The concept of CSF-SHBG originating from plasma by restricted diffusion is strongly supported by the finding that the CSF/plasma ratio of SHBG is independent of the plasma-SHBG concentration in the entire physiological range. Possible diagnostic and pathophysiological implications of this so far undetected CSF-constituent are discussed with regard to neurological and endocrine abnormalities.