Effect of diets supplemented with different conjugated linoleic acid (CLA) isomers on protein expression in C57/BL6 mice.

BACKGROUND: The individual genetic variations, as a response to diet, have recently caught the attention of several researchers. In addition, there is also a trend to assume food containing beneficial substances, or to supplement food with specific compounds. Among these, there is the conjugated linoleic acid (CLA), which has been demonstrated to reduce fat mass and to increase lean mass, even though its mechanism of action is still not known. We investigated the effect of CLA isomers (CLA c9,t11 and CLA t10,c12) on the proteomic profile of liver, adipose tissue, and muscle of mouse, with the aim of verifying the presence of a modification in fat and lean mass, and to explore the mechanism of action. METHODS: C57/BL6 mice were fed for 2 months with different diets: (1) standard chow, (2) CLA c9,t11 diet, (3) CLA t10,c11 diet, (4) CLA isomers mixture diet, and (5) linoleic acid diet. The proteomic profile of liver, white adipose tissue, and muscle was investigated. Statistical significance of the spots with an intensity higher than twofold in expression compared to the control was tested using student's t test (two-tail). RESULTS: We found that both isomers modulate the proteomic profiles of liver, adipose tissue, and muscle by different mechanisms of action. Liver steatosis is mostly due to the isomer CLA t10,c12, since it alters the expression of lipogenetic proteins; it acts also reducing the adipose tissue and increasing fatty acid oxidation in muscle. Conversely, CLA c9,t11 has no relevant effects on liver and adipose tissue, but acts mostly on muscle, where it enhances muscular cell differentiation. CONCLUSIONS: Administration of CLA in humans has to be carefully personalized, since even considering the presence of a species-specific effect, adverse effects might occur on long-term supplementation. Here we demonstrated that, in mouse, CLA is effective in reducing fat mass, but it also induces liver steatosis. The increase of lean mass is linked to an induction of cell proliferation, which, on long-term supplementation, might also lead to adverse effects.

Conjugated linoleic acid isomers modulate protein expression profile in rat hepatocytes.

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid, which has been recently proven to be effective in reducing body fat mass, but brings as a side effect, the liver enlargement due to an increased lipid content. The in vivo lipogenic activity has been suggested to be due to the reduction in fat mass and to the consequent metabolism of blood glucose to fatty acid in the liver rather than in the adipose tissue. We investigated the ability of CLA to directly induce steatosis by modulating the expression pattern of hepatic proteins involved in lipid metabolism. To avoid interferences derived from CLA metabolism by other tissues, we used the in vitro model of freshly isolated rat hepatocytes incubated in the presence of different CLA isomers. The direct effect of CLA on lipid accumulation in hepatocytes was demonstrated by the altered expression pattern of several proteins involved in lipid metabolism, as assessed by two-dimensional gel electrophoresis and confirmed by Western blotting analysis. The CLA isomer c9,t11 was most effective in modulating the protein expression profile.

Alpha-2 adrenergic activity in perimenopausal women.

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F = 0.7, p = NS; F = 0.2, p = NS and F = 0.1, p = NS respectively) between PeriMW both before and after therapy and PreMW. Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F = 0.8, p = NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F = 12; p < 0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F = 1.2, p = NS; F = 0.5, p = NS and F = 1.3, P = NS respectively). HR decreased significantly after clonidine in PreMW (F = 5.4, p < 0.03) but not in PeriMW before (F = 1.0, p = NS) and during estrogen therapy (F = 0.5, p = NS). Clonidine did not affect plasma E in the three groups studied (F = 2.8, p = NS; F = 2.2, P = NS and F = 0.1, p = NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

Effect of estradiol on the sympathoadrenal response to mental stress in normal men.

It has been shown that steroid hormones are able to influence the sympathoadrenal system activity. Therefore, we have investigated in a double blind cross-over study the effect of percutaneous estradiol administration (100 micrograms) on the sympathoadrenal and cardiovascular responses to mental arithmetic stress in 20 normal young males. The plasma estradiol level was 154 +/- 14 pmol/L during the estrogen session (ES) and 44 +/- 7 pmol/L during the placebo session (PL; P < 0.001). The mental stress induced a significant increase in systolic blood pressure during both the PL (F = 7.2; P < 0.001) and the ES (F = 4.8; P < 0.01); the peak obtained during PL was, however, higher than that during ES (128 +/- 2 vs. 122 +/- 3 mm Hg; P < 0.02). A significant increase in pulse rate was observed during PL (F = 4.2; P < 0.002), but not during ES (F = 2.6; P = 0.47), with the peak pulse rate being higher during mental stress in the PL than the ES (78 +/- 2 vs. 74 +/- 2 beats/min; P < 0.03). In response to the mental stress, plasma epinephrine increased significantly during PL (F = 3.2; P < 0.03), but not during ES (F = 1.1; P = 0.3). The stress-induced peak in plasma epinephrine during PL was higher than that during ES when expressed as the absolute value or the incremental peak (513 +/- 103 vs. 125 +/- 32 pmol/L; P < 0.005). The incremental peak in plasma norepinephrine obtained during PL was higher than that during ES (0.78 +/- 0.1 vs. 0.27 +/- 0.07 nmol/L; P < 0.02). Plasma free fatty acid, acetoacetate, and 3-hydroxybutyrate increased significantly from basal values during PL, but not during ES. These data show that mildly elevated levels of estradiol are able to influence the response of the adrenal medulla to mental stress in men.

Plasma catecholamines after thyrotropin-releasing hormone administration in hypothyroid patients before and during therapy.

In order to investigate sympathoadrenal activity in hypothyroidism we studied the cardiovascular and catecholamine responses to thyrotropin-releasing hormone (TRH) infusion in nine hypothyroid patients before and during adequate therapy and in seven healthy subjects. We evaluated mean arterial pressure, heart rate, plasma epinephrine and norepinephrine levels after TRH administration (200 micrograms iv) in the three groups. Mean arterial pressure, heart rate and plasma epinephrine levels were not different in the three groups and did not change after TRH administration. Hypothyroid subjects showed increased plasma norepinephrine levels (1.48 +/- 0.15 nmol/l), which were reduced after euthyroidism was reached (0.84 +/- 0.11 nmol/l) (p < 0.01). An exaggerated response of norepinephrine to TRH was observed in hypothyroid patients before therapy (incremental peak (IP) = 0.59 +/- 0.13 nmol/l) but not in hypothyroid patients during therapy (IP = 0.19 +/- 0.02 nmol/l p < 0.02) or in the control group (IP = 0.15 +/- 0.04 nmol/l; p < 0.05). This study indicated that TRH administration is able to influence the sympathetic activity during hypothyroidism in humans.

Alpha 2-adrenergic activity is normal in patients with thyroid disease.

OBJECTIVE: Several studies indicate an inverse relationship between the sympathetic nervous system activity and thyroid function. Altered adrenoceptor sensitivity, particularly alpha 1 and beta, have been described in hypothyroid and hyperthyroid patients. No information in patients with thyroid disease is available on the main mechanism regulating sympathetic nervous system outflow, i.e. the alpha 2-adrenoceptor pathway. In our study we evaluated alpha 2-adrenergic activity in patients with thyroid disease by the assessment of cardiovascular and catecholamine response to clonidine, a central alpha 2 adrenergic agonist. PATIENTS: Ten patients with hypothyroidism, six patients with hyperthyroidism before and during adequate therapy, and ten healthy subjects. MEASUREMENTS: After three blood samples for the basal determination of noradrenaline and adrenaline, the subjects swallowed 4 micrograms/kg body weight of clonidine. Blood pressure and pulse rate were measured 30, 60, 90, 120, 130 and 140 minutes after clonidine administration; blood samples for determination of catecholamines were drawn at 120, 130 and 140 minutes. RESULTS: At presentation the decrease in plasma noradrenaline after clonidine in the patients was similar to that of the control group (hypothyroids: 1.07 +/- 0.23 nmol/l mean +/- SEM; hyperthyroids: 0.54 +/- 0.06 nmol/l; controls; 0.36 +/- 0.10 nmol/l; F = 1.2, P = NS). No differences were detected in the fall in adrenaline and mean arterial pressure (MAP) after clonidine. The adequate therapy induced in hypothyroid patients a decrease in the basal levels of noradrenaline (1.88 +/- 0.28 vs 0.67 +/- 0.10 nmol/l; P < 0.05) and a lesser fall in mean arterial pressure after clonidine (delta MAP 20.4 +/- 2.0 vs 9.7 +/- 2.8 mmHg; P < 0.05). No variations were detected in hyperthyroid patients after therapy either in basal hormones levels or in the magnitude of decrement in MAP and noradrenaline induced by clonidine. CONCLUSIONS: We conclude that in spite of the previously reported abnormalities in alpha 1 and beta-adrenergic receptor activity, the inhibitory alpha 2-receptor pathway is normal in patients with altered thyroid function.

Sex differences in catecholamine response to clonidine.

Sex-related differences both in the basal secretion of catecholamines and in the adrenergic reactivity to various stimuli have been described. We studied the responses of catecholamines and arterial blood pressure to clonidine (0.3 mg per os) in 31 normotensive subjects (10 men (M), aged 18-42 years, and 21 women (W), aged 20-48 years). Plasma catecholamines were determined by HPLC at -30, -15, 0, 120, 130, 140 min after clonidine. The basal levels of plasma norepinephrine were similar in men and in women (M = 1.16 +/- 0.26 vs. W = 0.87 +/- 0.07 nmol/l). Basal plasma epinephrine levels were not different in the two sexes (M = 0.21 +/- 0.03 vs. W = 0.14 +/- 0.03 nmol/l). The mean arterial pressure decrease after clonidine was similar in the two groups (M = 13 +/- 3 vs. W = 15 +/- 2 mmHg). The decrease in plasma epinephrine after clonidine was similar in men and women (M = 0.06 +/- 0.04 vs. W = 0.09 +/- 0.02 nmol/l). In contrast, the plasma levels of norepinephrine after clonidine were reduced more in women than in men either when expressed as absolute values (W = 0.63 +/- 0.07 vs. M = 0.3 +/- 0.1 nmol/l; F = 7.6, P < 0.02) or as percentage change (W = 71 +/- 3 vs. M = 34 +/- 8; P < 0.002). The present study demonstrates that an elevated alpha 2-adrenergic activity in women may be responsible for the sexual dimorphism in catecholamine secretion.

Daily variations in catecholamine excretion are not influenced by very low calorie diet in obese women.

The increase in metabolic efficiency during energy restriction seems to be an established phenomenon in obese patients. The sympathoadrenal system is involved in the control of energy expenditure and the catecholamine responses to stimuli vary during the day. We therefore studied the circadian pattern of urinary catecholamine excretion during 4-h collections for two consecutive days in a group of 20 obese female patients during and after a very low calorie diet (500 kcal/die). The diet period induced a significant weight loss in all the patients studied (99.1 +/- 3.7 vs 92.5 +/- 4.1 Kg; p < 0.01). The mean daily excretion of epinephrine did not change after 24 days of diet restriction when compared with the value obtained at the 4th day (12.0 +/- 2.5 vs 10.3 +/- 2.2 nmol/4 h respectively; p = NS) while a slight decrease was observed in the mean daily excretion of norepinephrine (52.5 +/- 8.7 vs 66.6 +/- 9.3 nmol/4 h respectively; p = NS). A circadian rhythm was detected for epinephrine and norepinephrine excretion both during and after very low calorie diet. No significant changes were found in the chronobiological characteristics of epinephrine and norepinephrine with the peak of excretion in the afternoon both during (epinephrine: 16:30 h; norepinephrine: 16:45 h) and after the diet (epinephrine: 17:35 h; norepinephrine: 18:00 h). It seems doubtful that alterations in the chronobiological pattern of catecholamines play a role in the metabolic adaptation occurring during very low calorie diet in obese females.

Effects of thyroid hormone status on the growth hormone responses to clonidine.

It has been shown that thyroid hormones are positive regulators of GH synthesis and secretion. The serum GH response to stimuli seems to be influenced either by sex or by spontaneous hypothalamic rhythm. The growth hormone responses to clonidine administration (4 micrograms/kg) have been therefore studied in a group of female patients with thyroid disease (seven hyperthyroid and five hypothyroid) before and after the achievement of the euthyroid state. In hyperthyroid patients both basal and clonidine-stimulated GH levels were similar to normal subjects; the achievement of euthyroidism did not modify the GH response to clonidine. Serum GH peaks after clonidine were lower in hypothyroids patients than in hyperthyroids and normal subjects; the GH response to alpha 2-agonist administration did not change during thyroid replacement therapy. The GH response to clonidine was not influenced by the GH secretory status in the preceding hour.

Sexual dimorphism of the autonomic nervous system response to weight loss in obese patients.

The sex-related response of the sympathoadrenal system to very low calorie diet (VLCD) with sodium restriction has been studied in a group of 16 obese subjects (8 men; 8 women). Once in sodium balance obese men were different from women in respect to initial body weight, mean daily 4 h urinary excretion of epinephrine (E) and norepinephrine (NE) measured for 48 h. After 20 days of VLCD the weight loss was higher in men than women (P < 0.01), E excretion increased in men more than in women (P < 0.01), and was correlated with weight decrement (r = 0.78; P < 0.01). NE excretion decreased in a similar way in both sexes. The present findings demonstrate sexual dimorphism in catecholamine excretion during VLCD and provide further evidence of the relative autonomy of adrenomedullary secretion from sympathetic nervous system activity.

Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients.

OBJECTIVE: To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control. RESEARCH DESIGN: The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control. RESULTS: The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels. CONCLUSION: We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes.

High urinary excretion of adrenaline in insulin dependent diabetic subjects.

In view of the hyperglycemic and ketogenic actions of catecholamines, studies on the adrenergic pattern in diabetic patients are relevant to the management of diabetes. We have studied urinary adrenaline and noradrenaline excretion in 4-hour collections in 16 type I diabetic male patients without signs of autonomic or peripheral neuropathy and 11 age-weight matched controls. In diabetic patients adrenaline levels were higher than control subjects (26.8 +/- 3.9 vs 10.7 +/- 3.0 nmol/4h; p < 0.003) but did not differ in respect of noradrenaline (62.6 +/- 6.8 vs 59.6 +/- 10.8 nmol/4h) and creatinine excretion. This finding demonstrates a hyperactivity of the adrenal medulla in diabetic patients without concomitant elevations of noradrenaline. This occurred in absence of hypoglycemia and seems to be a common feature of type I diabetics without complications. Since these levels of adrenaline are sufficient to stimulate both lypolysis and glycogenolysis a previous characterization of adrenomedullary activity may help to better define insulin demands in diabetic patients.

Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia.

In 10 obese, new-onset non-insulin-dependent diabetes mellitus (NIDDM) patients (group A), continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia during 14 days. Fasting blood glucose was 4.6 +/- 0.2 mmol/L and mean daily blood glucose 5.8 +/- 0.2 mmol/L at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U of insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 hours. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 18.5 +/- 0.12 to 7.9 +/- 0.25 nmol/24 hours. Gliclazide was given to group A following CSII, and to five obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A, and induced in group B, excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to intravenous glucose, and significant increases in the mean-daily-insulin to mean-daily-blood-glucose ratio, as well as in the 24-hour urinary C-peptide-to-glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on efficacy of endogenous insulin (slope of disappearance of blood glucose divided by insulin levels). During 6 months of gliclazide treatment, excellent glycemic control was maintained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose, and augmented mean 48-hour insulin-to-glucose and urinary C-peptide-to-glucose ratios. No change in the ratio of glucose disposal to endogenous insulin was noted. We conclude that physiologic insulin replacement may induce normoglycemia in NIDDM, indicating that insulin resistance is not of clinical significance; gliclazide has a beta-cell-stimulating action that is maintained quantitatively unchanged for at least 6 months; the therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on the gliclazide action.

Effect of 6 months' gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial CSII-induced normoglycemia.

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.

Chronobiology of catecholamine excretion in normal and diabetic men.

The adrenomedullary response to stimuli is often elevated in poorly controlled insulin dependent diabetic patients, and it is controversial whether the adrenomedullary hyperactivity induces the suppression of the circadian rhythm of catecholamines. We have studied the urinary excretion of catecholamines in 11 diabetic patients during 48 h in 4-h collections. Eleven age and weight matched normal subjects served as controls. A circadian rhythm was detected for adrenaline and noradrenaline excretion both in normal and diabetic subjects, with the highest value for both catecholamines in the early afternoon. The mean daily adrenaline levels were significantly higher in diabetic than in control subjects (p less than 0.05). The dopamine excretion was correlated with noradrenaline excretion in normal subjects but did not show a definite circadian rhythm. We conclude that the adrenomedullary hyperactivity does not affect the rhythmic fluctuations of adrenaline and noradrenaline. The dopamine excretion does not show circadian variations and this probably reflects the absence of a single controlling oscillator.

Effects of androgen treatment in impotent men with normal and low levels of free testosterone.

The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimum serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens.

Adrenomedullary hyperactivity in type I diabetic patients before and during continuous subcutaneous insulin treatment.

Urinary norepinephrine (NE) and epinephrine (E) excretion was measured at 4-h intervals for 2 consecutive days in nine type I diabetic patients with no signs of autonomic neuropathy before and after 3 weeks of glycemic control with continuous insulin infusion (CSII). Twenty-four-hour urinary E excretion was significantly higher in the diabetic patients than in normal subjects both before and after the period of CSII treatment [mean, 198.9 +/- 20.6 +/- SE and 127.8 +/- 24.4 vs, 46.6 +/- 9.8 nmol/day; P less than 0.05 for both]. The values in each of the 4-h periods before and in two of three of the periods after the 3-week period of CSII were significantly higher than those in normal subjects. Total urinary NE excretion was similar to that in the normal subjects at both times. The 24-h urinary NE/E ratio was significantly lower in diabetic patients even after they had achieved good metabolic control, compared with that in normal subjects (1.4 +/- 0.2 vs, 11.6 +/- 3.7; P less than 0.03). These data demonstrate hyperactivity of the adrenal medulla in type I diabetic patients, which is only partially reversed by a short period of glycemic control.

Changes in the bioactivity to immunoreactivity ratio of circulating luteinizing hormone in impotent men treated with testosterone undecanoate.

Testosterone undecanoate was administered orally (80 mg twice daily) for 30 days to 10 impotent men with mild Leydig cell failure, age 28 to 42 years. Placebo was administered for 30 days both before and at the end of testosterone undecanoate therapy. Serum levels of bioactive LH, immunoreactive LH and testosterone were determined in basal conditions (day zero), 30 days after the first placebo administration, at the 15th and 30th day of testosterone undecanoate therapy, and at the end of the second treatment with placebo (90th day). Bioactive LH was measured by a sensitive and specific in vitro bioassay based on testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH and testosterone were determined by a double-antibody RIA technique. The results were compared with those obtained in 30 untreated normal young men. In the basal state, serum concentrations of immunoreactive LH were significantly higher in the patients (P less than 0.02) than in control subjects, whereas testosterone levels were significantly lower (P less than 0.001) in the impotent men. In contrast, bioactive LH levels and the bioactive LH to immunoreactive LH ratios were similar in the two groups. In the patients, at the 15th day of treatment with testosterone undecanoate, serum levels of testosterone and bioactive LH were significantly higher (P less than 0.01) than basal values, whereas immunoreactive LH concentrations showed no significant changes. Consequently, the bioactive LH to immunoreactive LH ratios rose significantly (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Very low calorie diet induces opposite effects on sympathetic nervous system and adrenomedullary responses.

The effect of very low calorie diet (VLCD) on catecholamine excretion during 24 h was examined in nine obese men, with normal blood pressure, maintained on low sodium balance, after 3 days and 14 days of the diet period. A significant decrease in the total daily noradrenaline (NA) excretion was observed at the end of the diet (P less than 0.05). The daily excretion of adrenaline (A) increased (P less than 0.05) with a fall in the NA/A ratio (5.1 +/- 2.6 vs 12.5 +/- 3.7; P less than 0.03). The results demonstrate that the sympathetic nervous system is influenced to a greater extent by caloric intake than sodium homeostasis and that the VLCD exerts different effects on SNS and adrenomedullary secretion.