Testosterone and Regional Fat Distribution

The effects of testosterone treatment of abdominally obese men have been assessed by evaluating the following parameters: The metabolic activity of different adipose tissue regions in vivo (using lipid label as a tracer) and in vitro (measuring lipoprotein lipase(LPL) activity), the total and visceral adipose tissue mass, insulin sensitivity, fasting blood glucose, blood lipids, and blood pressure as well as prostate volume. Middle-aged men with abdominal obesity were treated with transdermal administration of testosterone (T), dihydrotestosterone (DHT) or placebo (P) during 9 months. The study was double-blind. Treatment with T was followed by an inhibited uptake of lipid label in adipose tissue triglycerides, a decreased LPL-activity and an increased turn-over rate of lipid label in the abdominal adipose tissue region in comparisons with the DHT and P groups. These effects on adipose tissue metabolism were not detected in the femoral adipose tissue region in any of the groups. T treatment was also followed by a specific decrease of visceral fat mass (measured by CT-scan), by increased insulin sensitivity (measured with the euglycemic glucose clamp), by a decrease in fasting blood glucose, plasma cholesterol and triglycerides as well as a decrease in diastolic blood pressure. In the DHT group an increased visceral mass was detected. No other changes in these variables were found in the DHT and P groups. There were no detectable changes in prostate volume (measured by ultra-sound), prostate specific antigen concentration, genito-urinary history or urinary flow measurements in any of the groups. It is suggested that T substitution to a selected group of men results in general metabolic and circulatory improvements. The prostate area needs further careful attention.     

No Specific Effect of Fluoxetine Treatment on Fasting Glucose,Insulin, Lipid Levels,and Blood Pressure in Healthy Men with Abdominal Obesity

In this paper we investigated the effect of fluoxetine (60 mg/d) on serum lipids, glucose and insulin concentrations and blood pressure by means of a randomized, double-blind placebo controlled trial. Thirty-eight overweight BMI: 26–30 kg/m²), nondiabetic, nonhypertensive men with an abdominal fat distribution (waist/hip ratio: >0.97) received dietary advice and placebo or fluoxetine for 12 weeks. The changes in serum parameters and blood pressure in the fluoxetine treated group were not different from the placebo treated group, despite a significantly larger weight loss in the fluoxetine group. In both groups serum total-cholesterol concentrations, serum LDL-cholesterol concentrations and tlie HDL/LDL ratio were significantly improved after treatment. Reductions in fasting glucose concentration and systolic blood pressure were only significant in the placebo group. A reduction of serum triglycerides and an increase of HDL-cholesterol were found in the fluoxetine treated group. In the total study population the changes in serum lipids seemed to be more strongly related to the change in total body fat or subcutaneous abdominal fat (assessed by MRI) compared to the change in visceral fat. The improvement of most of the serum lipids was related to tlie change in total body fat independent of the mechanism for attaining this fat loss. Our results indicate that fluoxetine treatment has no specific effect beyond that expected for weight loss on serum lipid, glucose and insulin concentrations, and blood pressure in overweight men.     

Testosterone Administration Decreases Generosity in the Ultimatum Game

How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants'' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man''s level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.     

Inhibition of 5alpha-reductase blocks prostate effects of testosterone without blocking anabolic effects

We studied the effect of the 5alpha-reductase inhibitor MK-434 on responses to testosterone (T) in orchiectomized (ORX) male Brown Norway (BN) rats aged 13 mo. At 4 wk after ORX or sham surgery, a second surgery was performed to implant pellets delivering 1 mg T/day or placebo pellets. During the second 4 wk of the study, rats received injections of MK-434 (0.75 mg/day) or vehicle injections. Treatment with T elevated serum T to 75% above that for sham animals (P = 0.002) and did not affect serum dihydrotestosterone (DHT) or serum estradiol. T treatment also caused an elevation of prostate T and a marked elevation of prostate DHT. During the second half of the study, ORX rats lost an average of 18.86 +/- 4.62 g body wt. T completely prevented weight loss, and the effect was not inhibited by MK-434 (P < 0.001). ORX produced a nonsignificant trend toward a small (5%) decrease in the mass of the gastrocnemius muscle (P = 0.0819). This trend was also reversed by T, and the effect of T was not blocked by MK-434. T caused a significant 16% decrease in subcutaneous fat that was not blocked by MK-434 (P < 0.05). Finally, T caused a 65% decrease in urine excretion of deoxypyridinoline, a marker of bone resorption, and again the effect was not blocked by MK-434 (P < 0.0001). In contrast, T caused a greater than fivefold increase in prostate mass, and the effect was almost completely blocked by MK-434 (P < 0.0001). This study demonstrates that 5alpha-reductase inhibitors may block the undesirable effects of T on the prostate, without blocking the desirable anabolic effects of T on muscle, bone, and fat.     

Relation between dose of bendrofluazide,antihypertensive effect,and adverse biochemical effects.

OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or placebo for 12 weeks. SETTING--General practices in Zealand, Denmark. PATIENTS--257 Patients with newly diagnosed or previously treated hypertension, aged 25-70, who had a mean diastolic blood pressure of 100-120 mm Hg after receiving placebo for six weeks. MAIN OUTCOME MEASURES--Reduction in diastolic blood pressure and changes in biochemical variables (potassium, urate, glucose, fructosamine, total cholesterol, apolipoprotein A I, apolipoprotein B, and triglyceride concentrations). RESULTS--All doses of bendrofluazide significantly reduced diastolic blood pressure to the same degree (10-11 mm Hg). Clear relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses.     

Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men

The concentrations of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione (A-dione), testosterone (T) and dihydrotestosterone (DHT) have been measured before and after castration in men and two animal models, namely the rat and the guinea pig. In adult men, the pre-castration levels of plasma DHEAS and DHEA were measured at 1839 +/- 320 and 2.4 +/- 0.5 ng/ml, respectively, while in both animal models, the concentrations of these two steroids were below 0.3 ng/ml. Orchiectomy in men reduced plasma T and DHT levels from 2.9 +/- 0.1 and 0.60 +/- 0.10 to 0.42 +/- 0.21 and 0.05 +/- 0.01 ng/ml (P less than 0.01), respectively, while there was no significant effect observed on DHEAS, DHEA and A-dione levels. By contrast, castration in the rat reduced the low levels of circulating DHEA and A-dione below the detection of the radioimmunoassay (RIA) used. In castrated guinea pig, a small quantity of plasma A-dione (0.07 +/- 0.02 ng/ml) was measured while DHEA was undetectable. Moreover, in the rat and guinea pig, plasma T and DHT levels became undetectable. Following administration of the antiandrogen Flutamide for two weeks in the castrated rat and guinea pig, prostate weight was not further reduced, thus indicating that there is no significant androgenic activity left following castration of these two species. In fact, castration in the rat and guinea pig caused a decrease in prostatic levels of DHT from 4.24 +/- 0.351 and 9.42 +/- 1.43 ng/g, respectively, to undetectable levels. In men, on the other hand, the prostatic DHT levels were only inhibited from 5.24 +/- 0.59 to 2.70 +/- 1.50 ng/g, respectively. As expected, when Flutamide was administered to the rat and the guinea pig, the levels of prostatic steroids remained undetectable while, in men, the DHT content in the prostate was further reduced to undetectable values. In summary, the plasma levels of DHEAS, DHEA, delta 4-dione are markedly different between men and both animal models used and furthermore, measurements of prostatic levels of androgens suggest that the high plasma levels of these steroids are likely responsible for the presence of important amounts of DHT in human prostate after castration.     

No effect of short-term testosterone manipulation on exercise substrate metabolism in men.

Compared with women, men use proportionately more carbohydrate and less fat during exercise at the same relative intensity. Estrogen and progesterone have potent effects on substrate use during exercise in women, but the role of testosterone (T) in mediating substrate use is unknown. The purpose of this investigation was to assess how large variations in the concentration of blood T would impact substrate use during exercise in men. Nine healthy, active men were studied in three distinct hormonal conditions: physiological T (no intervention), low T (pharmacological suppression of endogenous T with a gonadotrophin-releasing hormone antagonist), and high T (supplementation with transdermal T). Total carbohydrate oxidation, blood glucose rate of disappearance, and estimated muscle glycogen use were assessed by using stable isotope dilution and indirect calorimetry at rest and while bicycling at approximately 60% of peak O2 consumption for 90 min. Relative to the physiological condition (T = 5.5 +/- 0.5 ng/ml), total plasma T was considerably suppressed in low T (0.8 +/- 0.1) and elevated in high T (10.9 +/- 1.1). Despite the large changes in plasma T, carbohydrate oxidation, glucose rate of disappearance, and estimated muscle glycogen use were very similar across the three conditions. There were also no differences in plasma concentrations of glucose, insulin, lactate, or free fatty acids. Plasma estradiol (E) concentrations were elevated in high T, but correlations between substrate use and plasma concentrations of T, E, or the T-to-E ratio were very weak (r2 < 0.20). In conclusion, unlike the effect of acute elevation in E to constrain carbohydrate use in women, acute changes in circulating T concentrations do not appear to alter substrate use during exercise in men.     

Long-term effects of testim(r) 1% testosterone gel in hypogonadal men

A new transdermal preparation, Testim(R) 1% testosterone gel, has recently become available for normalization of serum testosterone in hypogonadal men. In short-term studies, it has been shown to reverse the clinical signs and symptoms of low testosterone and to be well tolerated with less applicationsite irritation than with testosterone patches. In 2 long-term studies with Testim, the predose early morning serum testosterone (T), dihydrotestosterone (DHT), and free testosterone (FT) levels were assessed. Serum T, DHT, and FT were all maintained in the normal range for up to 12 months. In these studies, involving a total of 371 hypogonadal men, evaluation by means of dual-energy x-ray absorptiometry revealed a significant increase from baseline in bone mineral density. A significant improvement was also observed in body composition (increased lean body mass, decreased fat mass, and decreased percentage fat). In addition, significant improvements in mood and sexual function were maintained for up to 12 months of treatment. The parameters measured included sexual performance, sexual motivation, sexual desire, and occurrence of spontaneous erections. These data from the 2 long-term studies support the results of the 90-day studies with Testim showing that the gel significantly improves the signs and symptoms associated with low testosterone compared with placebo. The data also support the conclusion that these improvements are maintained for up to 1 year of additional treatment.     

Subcutaneous obesity is not associated with sympathetic neural activation

We tested the hypothesis that muscle sympathetic nerve activity (MSNA) would not differ in subcutaneously obese (SUBOB) and nonobese (NO) men with similar levels of abdominal visceral fat despite higher plasma leptin concentrations in the former. We further hypothesized that abdominal visceral fat would be the strongest body composition- or regional fat distribution-related correlate of MSNA among these individuals. To accomplish this, we measured MSNA (via microneurography), body composition (via dual-energy X-ray absorptiometry), and abdominal fat distribution (via computed tomography) in 15 NO (body mass index 0.05, respectively) despite approximately 2.6-fold higher (P < 0.05) plasma leptin concentration in the SUBOB men. Furthermore, abdominal visceral fat was the only body composition- or regional fat distribution-related correlate (r = 0.45; P < 0.05) of MSNA in the pooled sample. In addition, abdominal visceral fat was related to MSNA in NO (r = 0.58; P = 0.0239) but not SUBOB (r = 0.39; P = 0.3027) men. Taken together with our previous observations, our findings suggest that the relation between obesity and MSNA is phenotype dependent. The relation between abdominal visceral fat and MSNA was evident in NO but not in SUBOB men and at levels of abdominal visceral fat below the level typically associated with elevated cardiovascular and metabolic disease risk. Our observations do not support an obvious role for leptin in contributing to sympathetic neural activation in human obesity and, in turn, are inconsistent with the concept of selective leptin resistance.     

Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells

Serum levels of the adrenal androgen dehydroepiandrosterone (DHEA) peak in men and women in the third decade of life and decrease progressively with age. Increasing numbers of middle-aged and older individuals consume over-the-counter preparations of DHEA, hoping it will retard aging by increasing muscle and bone mass and strength, decreasing fat, and improving immunologic and neurobehavioral functions. Because DHEA can serve as a precursor to more potent androgens and estrogens, like testosterone (T), dihydrotestosterone (DHT), and 17beta-estradiol (E2), supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer. The steroid-responsive human LNCaP prostate cancer cells, containing a functional but mutated androgen receptor (AR), were used to compare effects of DHEA with those of T, DHT, and E2 on cell proliferation and protein and/or gene expression of AR, prostate-specific antigen (PSA), IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-binding proteins-2, -3, and -5, (IGFBPs-2, -3, and -5), and estrogen receptor-beta (ERbeta). Cell proliferation assays revealed significant stimulation by all four steroids. DHEA- and E2-induced responses were similar but delayed and reduced compared with that of T and DHT. All four hormones increased gene and/or protein expression of PSA, IGF-IR, IGF-I, and IGFBP-2 and decreased that of AR, ERbeta, IGF-II, and IGFBP-3. There were no significant effects of hormone treatment on IGFBP-5 mRNA. DHEA and E2 responses were similar, and distinct from those of DHT and T, in time- and dose-dependent studies. Further studies of the mechanisms of DHEA effects on prostate cancer epithelial cells of varying AR status, as well as on prostate stromal cells, will be required to discern the implications of DHEA supplementation on prostatic health.     

Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice

Objective : To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor α stimulation results in reduced fat mass in men. Research Methods and Procedures : Orchidectomized mice were treated with the non‐aromatizable androgen 5α‐dihydrotestosterone (DHT), 17β‐estradiol, or vehicle. VO₂, VCO₂, resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. Results : DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high‐density lipoprotein‐cholesterol and triglyceride levels associated with markedly decreased 7α‐hydroxylase gene expression, indicating decreased bile acid production. Discussion : We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.     

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5α-reduction to form more potent androgens. We tested the hypothesis that trenbolone-enanthate (TREN) might prevent orchiectomy-induced losses in muscle and bone and visceral fat accumulation without increasing prostate mass or resulting in adverse hemoglobin elevations. Male F344 rats aged 3 mo underwent orchiectomy or remained intact and were administered graded doses of TREN, supraphysiological testosterone-enanthate, or vehicle for 29 days. In both intact and orchiectomized animals, all TREN doses and supraphysiological testosterone-enanthate augmented androgen-sensitive levator ani/bulbocavernosus muscle mass by 35-40% above shams (P ≤ 0.001) and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses (P < 0.05) and visceral fat accumulation (P < 0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at sham levels in both intact and orchiectomized animals, whereas supraphysiological testosterone-enanthate and high-dose TREN elevated prostate mass by 84 and 68%, respectively (P < 0.01). In summary, low-dose administration of the non-5α-reducible androgen TREN maintains prostate mass and hemoglobin concentrations near the level of shams while producing potent myotrophic actions in skeletal muscle and partial protection against orchiectomy-induced bone loss and visceral fat accumulation. Our findings indicate that TREN has advantages over supraphysiological testosterone and supports the need for future preclinical studies examining the viability of TREN as an option for androgen replacement therapy.     

Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes.

It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the effects of exercise without weight loss on total and regional adiposity and skeletal muscle mass and composition in lean men and in obese men with and without T2D. Twenty-four men participated in 13 wk of supervised aerobic exercise, five times per week for 60 min at a moderate intensity (approximately 60% peak oxygen uptake). Total and regional body composition was measured by magnetic resonance imaging. Skeletal muscle composition was determined using computed tomography. Cardiorespiratory fitness was assessed using a graded maximal treadmill test. Body weight did not change within any group in response to exercise (P > 0.1). Significant reductions in total, abdominal subcutaneous, and visceral fat were observed within each group (P < 0.01). The reduction in total and abdominal subcutaneous fat was not different (P > 0.1) between groups; however, the reduction in visceral fat was greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A significant (P < 0.01) increase in total skeletal muscle, high-density muscle area, and mean muscle attenuation was observed independent of group, and these changes were not different between groups (P > 0.1). Accordingly, whole body fat-to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion, regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.     

Treatment of Hypogonadism with Testosterone in Patients with Type 2 Diabetes Mellitus

ObjectiveTo investigate the effect of testosterone treatment on insulin resistance, glycemic control, and dyslipidemia in Asian Indian men with type 2 diabetes mellitus (T2DM) and hypogonadism.MethodsWe conducted a double-blind, placebo-controlled, crossover study in 22 men, 25 to 50 years old, with T2DM and hypogonadism. Patients were treated with intramuscularly administered testosterone (200 mg every 15 days) or placebo for 3 months in random order, followed by a washout period of 1 month before the alternative treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostasis model assessment [HOMA] in those patients not receiving insulin), fasting blood glucose, and hemoglobin A1c. The secondary outcomes were changes in fasting lipids, blood pressure, body mass index, waist circumference, waist-to-hip ratio, and androgen deficiency symptoms. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared with the effect of testosterone.ResultsTreatment with testosterone did not significantly influence insulin resistance measured by the HOMA index (mean treatment effect, 1.67 ± 4.29; confidence interval, -6.91 to 10.25; P > .05). Mean change in hemoglobin A1c (%) (-1.75 ± 5.35; -12.46 to 8.95) and fasting blood glucose (mg/dL) (20.20 ± 67.87; -115.54 to 155.94) also did not reach statistical significance. Testosterone treatment did not affect fasting lipids, blood pressure, and anthropometric determinations significantly.ConclusionIn this study, testosterone treatment showed a neutral effect on insulin resistance and glycemic control and failed to improve dyslipidemia, control blood pressure, or reduce visceral fat significantly in Asian Indian men with T2DM and hypogonadism. (Endocr Pract. 2010;16:570-576)     

Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men

Chronic hyperglycemia inhibits the male gonadal axis. The present analyses test the hypothesis that acute glucose ingestion also suppresses LH and testosterone (T) secretion and blunts the LH-T dose-response function. The design comprised a prospectively randomized crossover comparison of LH and T secretion after glucose vs. water ingestion in a Clinical Translational Research Center. The participants were healthy men (n = 57) aged 19-78 yr with body mass index (BMI) of 20-39 kg/m(2). The main outcome measurements were deconvolution and LH-T dose-response analyses of 10-min data. LH-T responses were regressed on glucose, insulin, leptin, adiponectin, age, BMI, and CT-estimated abdominal visceral fat. During the first 120 min after glucose ingestion, for each unit decrease in LH concentrations, T concentrations decreased by 86 (27-144) ng/dl (r = 0.853, P < 0.001). Based upon deconvolution analysis, glucose compared with water ingestion reduced 1) basal (nonpulsatile; P < 0.001) and total (P < 0.001) T secretion without affecting pulsatile T output and 2) pulsatile (P = 0.043) but not basal LH secretion. By multivariate analysis, pulsatile LH secretion positively predicted basal T secretion after glucose ingestion (r = 0.374, P = 0.0042). In addition, the glucose-induced fall in pulsatile LH secretion was exacerbated by higher fasting insulin concentrations (P = 0.054) and attenuated by higher adiponectin levels (P = 0.0037). There were no detectable changes in the analytically estimated LH-T dose-response curves (P > 0.30). In conclusion, glucose ingestion suppresses pulsatile LH and basal T secretion acutely in healthy men. Suppression is influenced by age, glucose, adiponectin, and insulin concentrations.     

Serum and saliva sex hormone levels in !Kung San men

Serum concentrations of testosterone (Tser), 5 alpha-dihydrotestosterone (DHT), estradiol 17 beta (E2), and free testosterone in saliva (Tsal) were determined by means of the radioimmunoassay method in 114 !Kung San men living in the Bushmanland district of Namibia. The healthy men (mean age 26.4 years) were asked about their dietary habits over the last two months and their acute alcohol intake during the 24 hours preceding the blood and saliva sampling. Although the sex hormone status of the !Kung lies within the range of normal men reported for Caucasoid samples, both Tser and Tsal exhibit relatively low concentrations in comparison to the great majority of published mean values. On the other hand, comparatively high DHT levels point to an elevated 5 alpha-reduction of testosterone to DHT in our sample. Estradiol concentrations show no deviation from normal values reported elsewhere for healthy young men. Different dietary habits of the !Kung lead to significant differences in their sex hormone status: both levels of Tsal and the androgen ratio Tsal/Tser decrease with increasing supplement of the traditional hunter-gatherer diet with domestic and Western food products. The amount of alcohol consumed during the day before the blood and saliva sampling shows a significant effect on the DHT metabolism, and the shorter the time after drinking, the greater decrease of DHT and DHT/E2 can be observed.     

Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats

A rare sugar, d-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of d-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% d-psicose or 5% d-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, d-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that d-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed d-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. d-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that d-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.     

Hyperthyroidism is associated with higher plasma endothelin-1 concentrations

The objective of this study was to determine the change of plasma endothelin (ET)-1 concentrations and insulin resistance index after therapy for hyperthyroidism. We studied 20 patients with hyperthyroidism (15 women and 5 men; age, 34.0 +/- 2.8 years), and 31 patients with euthyroid goiters as controls (27 women, 4 men; age, 37.0 +/- 2.4 years). All hyperthyroid patients were treated with antithyroid drugs. The patients received evaluations before and after normalization of thyroid function. The evaluations included body mass index (BMI), body fat, and measurement of circulating concentrations of thyroid hormones, glucose, insulin, and ET-1. Hyperthyroid subjects had higher plasma ET-1 concentrations than the control group (P < 0.001). No significant differences in serum glucose and insulin concentrations or insulin resistance index estimated by the R value of the homeostasis model assessment (HOMA-R) were noted between the groups. Plasma ET-1 concentrations decreased after correction of hyperthyroidism compared with pretreatment (P = 0.006). Serum glucose concentrations decreased after correction of hyperthyroidism (P = 0.005). Moreover, both body weight-adjusted insulin concentrations and the HOMA-R index were also decreased after correction of hyperthyroidism compared with pretreatment (P = 0.026 and P = 0.019, respectively). Pearson's correlation revealed that plasma ET-1 levels positively correlated with serum triiodothyronine (T3) and free thyroxine (FT4) levels. Serum insulin levels and the HOMA-R index positively correlated with BMI and body fat. The HOMA-R index also positively correlated with serum T3 and FT4 levels. Neither insulin levels nor the HOMA-R index correlated with ET-1 levels. Hyperthyroidism is associated with higher plasma ET-1 concentrations. In addition, correction of hyperthyroidism is also associated with a decrease of plasma ET-1 levels as well as the insulin resistance index calculated by HOMA-R.     

Inhibin activity of the organs of the male reproductive system in rats treated with dihydrotestosterone

The content of protein hormone, inhibin, in the rat testis and prostate has been studied on preadolescent female mice. Both organs were characterized by a certain inhibin activity, it being higher in the prostate. A single injection of 25 mu kg dihydrotestosterone (DHT) to rats has been followed by the increase in testicular and prostate mass, elevation of 17 alpha-hydroxyprogesterone and testosterone levels in peripheral blood, and a slight rise in inhibin testicular activity, with the lack of these changes in the prostate. The detection of inhibin in the prostate confirms possible direct link of the organ with the pituitary body. DHT effect on spermatogenesis has been but insignificantly related to FSH depression.     

Effects of sex steroid implants on reproductive tissues of female garter snakes (Thamnophis sirtalis)

Female Thamnophis sirtalis were administered intraperitoneal implants of either estradiol 17β (E2), testosterone (T), 5α-dihydrotestosterone (DHT), or empty silastic capsules for 3 weeks. Plasma levels of E2 and T, measured by specific radioimmunoassay, were significantly elevated in E2 and T-implanted females when compared to controls. T-implanted females did not have elevated circulating E2 levels, suggesting that E2 in the plasma normally is not derived from peripheral conversion of T to E2. Implantation of DHT did not significantly change circulating levels of E2, T, or DHT. All three sex steroid—treated groups of animals had increased oviductal mass compared to controls, while hepatic mass of only E2-treated animals was significantly greater. None of the steroid treatments influenced ovarian mass. Oviductal epithelial cell height and area were greater in the three steroid-treated groups. Testosterone increased myometrial area while DHT drastically altered oviductal morphology. Hepatic cell area and number increased significantly in E2-treated females. However, a small increase in both hepatic cell area and number was noted in T- and DHT-treated females as well. These results suggest that androgen in both an aromatizable and non-aromatizable form can affect the oviduct of females but that the liver primarily responds to estrogenic steroids. © 1992 Wiley-Liss, Inc.