Omental and subcutaneous adipose tissue steroid levels in obese men

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.     

Intratesticular steroid levels and their hormonal control

Litter-mate adult male rats were treated with daily intramuscular injections of ACTH (10.5 micrograms), dexamethasone (2.0 mg), ethynyl estradiol (1.7 micrograms) and hCG (5 IU) for three consecutive days. The animals were sacrificed on the fourth day and the intratesticular and peripheral plasma steroid levels were analyzed. The steroids measured by radioimmunoassay included pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and dihydrotestosterone. In addition, the sulphoconjugated forms of pregnenolone, dehydroepiandrosterone, testosterone and dihydrotestosterone were estimated in the peripheral blood. The administration of ACTH diminished the intratesticular levels of all steroids studied. Also dexamethasone and ethynyl estradiol treatment suppressed all intratesticular steroid levels, except that of pregnenolone (the former) and of 17-hydroxyprogesterone (the latter). The suppressive effect of ethynyl estradiol was strongest on the levels of the delta 5-steroids and that of dexamethasone on the delta 4-steroids; the latter was significantly stronger than the effect of ACTH. The stimulatory effect of hCG was limited to the metabolism of progesterone and was restricted to the sequence: 17-hydroxyprogesterone----androstenedione----testosterone---- dihydrotestosterone. Dexamethasone-suppression, and hCG-stimulation of the intratesticular levels of delta 4-steroids, was mirrored by corresponding changes in the peripheral plasma levels, with the exception of the plasma levels of androstenedione which were not influenced by any of the treatments studied. Also the suppression of intratesticular testosterone and dihydrotestosterone levels by ACTH, dexamethasone, or ethynyl estradiol was closely reflected by their plasma levels both in the unconjugated and sulphoconjugated forms. On the hand, the administration of ACTH diminished the intratesticular levels of pregnenolone and progesterone but significantly increased those in the plasma. Moreover, both ACTH and ethynyl estradiol reduced the levels of all delta 5-steroids in testicular tissue, but not in the peripheral plasma, although they decreased the circulating levels of pregnenolone sulphate and dehydroepiandrosterone sulphate. The data are interpreted as suggesting that the hormonal agents studied interfere with testicular steroidogenesis through different mechanisms.     

Plasma levels of C19 steroid glucuronides in pre-menopausal women with non-classical congenital adrenal hyperplasia.

Recent reports have thrown doubt on the role of measurements of plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG) as a marker of peripheral androgen metabolism in women with polycystic ovarian syndrome and idiopathic hirsutism. It has been suggested that a plasma profile of C19 steroid glucuronides may be more informative. While preliminary data indicates that both 3 alpha-diolG and androsterone G (ADTG) may arise from adrenal steroid precursors, there have been no reports of C19 steroid glucuronides in women with non-classical, or late-onset congenital adrenal hyperplasia (NC-CAH), who constitute a significant proportion of the hirsute female population. We therefore measured plasma levels of 3 alpha-diolG, ADTG and dihydrotestosterone G (DHTG) before and following a standard Cortrosyn test in 15 symptomatic and 3 asymptomatic NC-CAH patients, 5 heterozygote carriers for 21-hydroxylase deficiency (NCHETS) and 18 normal women. The effects of chronic glucocorticoid (GCR) therapy (greater than 3 months) on the C19 steroid glucuronide profile in the symptomatic patients was also investigated. Baseline plasma levels of all 3 glucuronides were significantly (P less than 0.001) higher in symptomatic patients compared with either normals or NCHETS. However, the order of discrimination was ADTG greater than 3 alpha-diolG greater than DHTG. There were no significant differences between steroid glucuronide levels for NCHET and normal women and the C19 steroid glucuronide concentrations for the asymptomatic NC-CAH patients were greater than 2 SD above the normal means. Moderate clinical improvement was observed in all patients receiving oral GCR therapy and was accompanied by approx. 80% suppression of the plasma levels of all 3 C19 steroid glucuronides. This contrasts with a mean suppression of androstenedione of only 50%. However, plasma levels of the C19 steroid glucuronides were not significantly increased in response to a short ACTH stimulation test. This may be explained by the fact that the androgen glucuronides are thought to be peripherally formed metabolites derived from unconjugated glandular secreted androgen precursors and thus their synthesis at 60 min following adrenal stimulation may lag substantially behind that of their respective precursors. There were significant linear correlations between the levels of all 3 glucuronides, but neither correlated with Ferriman-Gallway scores, body mass index or 17-hydroxyprogesterone levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nature of changes in the level of steroid hormones and their precursors in peripheral blood of Papio monkeys under stress]

The radioimmunological method was applied to determination of changes in the peripheral blood plasma level of 12 steroids in male Papio hamadryas under immobilization and surgical stress. Androgen content decreased, and the concentration of steroid hormone precursors and hydrocortisone blood plasma content rose in response to stress. These changes were in contraphase with the circadian steroid rhythms. The most objective and sensitive criteria of the stress situation evaluation were decrease of testosterone and dihydrotestosterone level, increase of pregnenolone concentration, as well as of 17-alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone in the blood plasma.     

Glycogen depletion during prolonged exercise: influence of glucose, fructose, or placebo

We examined the influence of various carbohydrates of fuel homeostasis and glycogen utilization during prolonged exercise. Seventy-five grams of glucose, fructose, or placebo were given orally to eight healthy males 45 min before ergometer exercise performed for 2 h at 55% of maximal aerobic power (VO2max). After glucose ingestion, the rises in plasma glucose (P less than 0.01) and insulin (P less than 0.001) were 2.4- and 5.8-fold greater than when fructose was consumed. After 30 min of exercise following glucose ingestion, the plasma glucose concentration had declined to a nadir of 3.9 +/- 0.3 mmol/l, and plasma insulin had returned to basal levels. The fall in plasma glucose was closely related to the preexercise glucose (r = 0.98, P less than 0.001) and insulin (r = 0.66, P less than 0.05) levels. The rate of endogenous glucose production and utilization rose similarly by 2.8-fold during exercise in fructose group and were 10-15% higher than in placebo group (P less than 0.05). Serum free fatty acid levels were 1.5- to 2-fold higher (P less than 0.01) after placebo than carbohydrate ingestion. Muscle glycogen concentration in the quadriceps femoris fell in all three groups by 60-65% (P less than 0.001) during exercise. These data indicate that fructose ingestion, though causing smaller perturbations in plasma glucose, insulin, and gastrointestinal polypeptide (GIP) levels than glucose ingestion, was no more effective than glucose or placebo in sparing glycogen during a long-term exercise.     

Influence of carbohydrate ingestion on oxidative stress and plasma antioxidant potential following a 3 h run

Concentrations of reactive oxygen species (ROS) increase during exercise secondary to increased oxygen uptake, xanthine oxidase activity, and immune system activation. Carbohydrate compared to placebo beverage ingestion is associated with an attenuated cortisol and catecholamine response. Catecholamines can undergo autooxidation to form ROS. We hypothesized that during intense exercise, ingestion of carbohydrate compared to placebo would diminish oxidative stress. Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% VO

2max

on two occasions while receiving carbohydrate or placebo beverages (1 l/h, double-blinded) in a randomized, counterbalanced order. Blood samples were collected before and immediately after exercise, snap frozen in liquid nitrogen, and stored at -80°C until analysis. Plasma samples were analyzed for F2-isoprostanes (FIP) and lipid hydroperoxides (ROOH) as measures for lipid peroxidation, ferric reducing ability of plasma (FRAP) as a measure of plasma antioxidant potential and for cortisol. The pattern of change in cortisol was significantly different between carbohydrate and placebo conditions (P=0.024), with post-exercise levels higher in the placebo condition. Under both carbohydrate and placebo conditions, significant increases in FIP, ROOH, and FRAP were measured, but the pattern of increase was not different (FIP, interaction effect, P=0.472; ROOH, P=0.572; FRAP, P=0.668). Despite an attenuation in the cortisol response, carbohydrate compared to placebo ingestion does not counter the increase in oxidative stress or modulate plasma antioxidant potential in athletes running 3 h at 70% VO

2max

.     

The effect of infusions of 5 alpha-dihydrotestosterone or estradiol-17 beta on the concentration of some steroids in the human testicular vein and artery

The concentrations of testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstan-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, estradiol-17 beta and testosterone-glucosiduronate were measured in the plasma of the testicular vein and artery simultaneously with the estimation in peripheral venous and arterial plasma 60 min after an infusion of 3000 micrograms dihydrotestosterone (DHT) or estradiol (E2), respectively, in patients undergoing orchiectomy for prostatic cancer. The results were as follows; following infusion of DHT or E2, both steroids were completely metabolized by the testes. After DHT the testicular secretion of E2 was significantly reduced. In peripheral plasma 3 alpha-diol concentration was increased. Following E2 a transient elevation of testosterone in the spermatic vein was observed, whereas a slight decrease of DHT and an increase especially of 3 beta-diol levels occurred. It is assumed that DHT as well as E2 plays a role as intratesticular regulator of steroid synthesis and metabolism.     

15-Keto-13,14-dihydroprostaglandin E2- and F2 alpha-metabolite levels in blood from men and women given prostaglandin E2 orally

Prostaglandin E2 (PGE2) was administered orally in a dose of 1 mg to healthy males (n = 20) and females (n = 10). Blood levels of 15-keto-13,14-dihydroprostaglandin F2 alpha (PGF2 alpha-M) and 15-keto-13,14-dihydroprostaglandin E2 (PGE2-M), determined as the rearrangement product 11-deoxy-15-keto-13,14-dihydro-11 beta, 16-cycloprostaglandin E2 (PGE2-cyclo-M), were measured. The levels of the two PG metabolites increased already 10 minutes after ingestion of the tablet and the mean peak value for PGE2-cyclo-M in the men was 4.64 nmol/l which was reached 50 minutes after PGE2 administration. The mean peak value in women was 4.99 nmol/l which was obtained after 30 minutes. The increase in PGE2-cyclo-M concentration was significantly faster (p less than 0.05) in women than in the men. The mean plasma concentration of PGF2 alpha in males were 0.20 nmol/l prior to treatment and rose after PGE2 ingestion to mean peak level of 0.84 nmol/l after 70 minutes. The corresponding values for the females were 0.18 nmol/l and 0.88 nmol/l 50 minutes into treatment. When the data from both sexes were amalgamated PGE2-cyclo-M peak levels were reached significantly (p = 0.004) sooner than the PGF2 alpha-M peak. The two PG metabolites returned to baseline levels in 70% of the individuals after 240 minutes. The increase in PGF2 alpha-M concentration following oral administration of PGE2 indicates that part of the PGE2 was reduced to PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.     

Plasma adrenocorticotropin and cortisol responses to brief high-intensity exercise in humans

The purpose of this study is to examine plasma cortisol and adrenocorticotropin (ACTH) levels following a brief high-intensity bout of exercise. Each subject (n = 6) performed a 1-min bout of exercise on a cycle ergometer at 120% of his maximum O2 uptake. Blood samples were collected at rest, immediately following the exercise bout, and at 5, 15, and 30 min postexercise. Mean (+/- SE) plasma ACTH levels increased significantly (P less than 0.05) from 2.2 +/- 0.4 pmol/l at rest to 6.2 +/- 1.7 pmol/l immediately following exercise. Mean (+/- SE) plasma cortisol levels increased significantly from 0.40 +/- 0.04 mumol/l at rest to 0.52 +/- 0.04 mumol/l at 15 min postexercise. These data show that brief high-intensity exercise results in significant increases in plasma cortisol and ACTH levels. Furthermore, the temporal sequence between the two hormones suggests that the increase in plasma cortisol levels following brief high-intensity exercise is the result of ACTH-induced steroidogenesis in the adrenal cortex.     

Neurotensin-like immunoreactivities in human plasma: feeding responses and metabolism

Feeding responses and day and night levels of plasma concentration of neurotensin (NT) and NT-fragments were studied in healthy subjects. Plasma levels were measured by three radioimmunoassays recognizing intact NT in addition to C- and N-terminal immunoreactivity. The metabolism of NT was studied following intravenous administration. In 106 subjects fasting levels of intact NT (median 18 pmol/l), C-terminal (median 30 pmol/l) and N-terminal immunoreactivity (median 95 pmol/l) were unrelated to sex or age. Postprandially plasma levels in seven subjects measured with all assays increased by a factor 1-3. Following a mixed meal the increase was biphasic, whereas the response to dairy cream was monophasic. Repetitive measurements during 24 hours showed that levels of N-terminal immunoreactivity fluctuated in a manner related to meal ingestion and were elevated throughout the daytime, whereas intact NT and C-terminal immunoreactivity changed little. Following intravenous infusion of 2.4 pmol/kg/min NT in 5 subjects the chromatographic pattern was similar to that seen postprandially. The plasma half life of intact NT and C-terminal immunoreactivity was 1.5 and 1.2 min, whereas that of N-terminal immunoreactivity was 10.0 min. The differences in circulating levels could be explained by these differences in metabolism, but the physiological significance remains to be elucidated.     

Characterization of human plasma neurotensin-like immunoreactivity after fat ingestion

The concentration of neurotensin-like immunoreactivity in plasma (p-NTLI) increases after the ingestion of food, and fat seems to be the most important nutrient. It is essential to characterize the NT species that are responsible for this postprandial rise of p-NTLI. After an overnight fast, two male and two female subjects therefore ingested 300 ml of cream (containing 40% (w/w) milk fat). Unextracted plasma samples were subjected to column chromatography and the eluates were analysed using four NT antisera having different specificities. The concentration of chromatographically identified NT(1-13) in peripheral plasma increased significantly from 3 pM in the fasting state to 26 pM 30 min after the ingestion of fat. The concentration of NT(1-8), which is probably a metabolite of NT(1-13), also increased markedly. No significant increase of smaller COOH-terminal sequences of NT was found. The results show that the plasma concentration of NT(1-13) may increase about tenfold following the ingestion of fat. This is further support for the hypothesis that NT(1-13) may function as a hormone.     

Plasma levels of n-decanoyl ghrelin, another acyl- and active-form of ghrelin, in human subjects and the effect of glucose- or meal-ingestion on its dynamics

Besides n-octanoyl ghrelin (O-ghrelin), there is another acyl-form of ghrelin; n-decanoyl ghrelin (D-ghrelin), which has a decanoic acid modification. In this study, we examined the kinetics of D-ghrelin immunoreactivity in human plasma in comparison to O-ghrelin or total ghrelin by using a D-ghrelin-specific radioimmunoassay. The dynamics of plasma D-ghrelin was assessed following glucose- or meal-ingestion in healthy, non-obese subjects (5 males and 5 females). Correlations were also analyzed between the levels of plasma D-ghrelin and anthropometric or metabolic indicators in healthy human subjects (n=111, BMI 17.4-34.3). The plasma levels of D-ghrelin, like O- or T-ghrelin, significantly declined (p<0.05 for male and p<0.01 for female) 60 min after the ingestion of glucose in non-obese subjects. However, in the same subjects, no significant decline was noted in the levels of D-ghrelin, unlike O- or T-ghrelin, upon the meal ingestion. A significant increase was observed in the proportion of plasma D-ghrelin levels to that of T-ghrelin (p<0.05) in the healthy human subjects as BMI increased, unlike the proportion of O-ghrelin to T-ghrelin, which did not change. Since D-ghrelin possesses almost the same potential as that of O-ghrelin with regard to the feeding-stimulation, these differences between the dynamics of D- and O-ghrelin in human plasma might influence appetite-control, especially in those with increased BMI.     

A physiological dose of estradiol with progesterone affects striatum biogenic amines

The acute effect of estradiol and progesterone on dopamine and serotonin metabolism in rat striatum was studied. One subcutaneous injection of 17 beta-estradiol (300 ng) and progesterone (150 micrograms) into intact male rats increased plasma levels of these steroids, while testosterone, corticosterone, and estrone remained unchanged. Dehydroepiandrosterone, androstane-3 beta, 17 beta-diol and dihydrotestosterone remained undetectably low. Prolactin decreased and androstane-3 alpha, 17 beta-diol, and 17-OH progesterone increased, but less than estradiol and progesterone. Peak levels of striatal dopamine, dihydroxyphenylacetic acid, and homovanillic acid were observed 15-45 min after steroid injection with a return to control values after 45-60 min, while serotonin and 5-hydroxyindoleacetic acid levels were slightly decreased. An injection of estradiol (70 ng) with progesterone (70 micrograms) to ovariectomized female rats left plasma prolactin levels unchanged, while striatum dopamine and serotonin as well as their metabolite concentrations peaked 15-60 min after steroid injection and returned to control values after 45-75 min. To allow for a better comparison of the action of these steroids, the effect of estradiol or progesterone alone and in combination on the brain of ovariectomized rats was compared in the same experiment. A similar increase in metabolites of dopamine levels was observed after these steroids alone or in combination, while dopamine levels were increased only after progesterone alone or in combination with estradiol. An injection of estradiol or progesterone to ovariectomized rats led to peak steroid concentrations at approximately the same time in the brain and plasma. In addition, plasma and brain steroid levels were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise on response of liver lipogenic enzymes to a high fructose diet.

Meal-fed Long-Evans rats fed a high fructose diet and exercised for 2-hr daily on a treadmill for three days had lower levels of several hepatic lipogenic enzymes (acetyl CoA carboxylase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme and citrate cleavage enzyme) than did sedentary rats pair-fed the diet. Accumulation of triglycerides in plasma following ingestion of a fat-free, high fructose meal and injection of Triton WR-1339, an inhibitor of plasma triglyceride clearance, was not significantly different in the two groups of animals. All of the hepatic lipogenic enzymes measured, with the exception of citrate cleavage enzyme, attained similar levels in the runners as in the controls after 5 days on the high fructose diet. Thus the exercise appeared to affect the time course of the increase in the levels of activity of most of the lipogenic enzymes but not the final steady state levels attained.     

Plasma levels of human neurotensin: methodological and physiological considerations

The ingestion of a meal high in fat content is known to increase circulating levels of neurotensin (NT) in humans. However, the magnitude of the postprandial rise of NT in the general circulation and its physiological significance have been subject of much debate. The present study examines circulating levels of NT in male volunteers prior to and following each of their three daily meals (ca. 31 g fat/meal). The response observed are also compared to that elicited by the direct instillation of intralipid (ca. 44 g fat) into the duodenum. NT levels were determined by radioimmunoassay of acid/acetone extracted plasma fractionated by high pressure liquid chromatography. Meals caused a significant but modest increase in NT levels, with the largest increment (ca. 4 fmol/ml) occurring after breakfast. In contrast, NT levels increased ca. 20 fmol/ml with intraduodenal instillation of lipid. The meal-stimulated increases in circulating NT measured here are 4- to 5-fold less than those reported by others, the difference most likely reflecting the lesser amount of lipid ingested. Previous studies provided subjects with single meals containing in excess of 120 g of fat; the 30 g of fat ingested by our subjects, ca. 33% of total caloric intake, is near that recommended by the U.S. Senate, Select Committee on Nutritional and Human Needs. These data show that diets with a reasonable fat content have only a modest effect on circulating levels of NT.     

Studies on lipoprotein and adrenal steroidogenesis: II. Utilization of low density lipoprotein- and high density lipoprotein-cholesterol for steroid production in functioning human adrenocortical adenoma cells in culture

We examined the utilization of human low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol for steroid production in primary monolayer culture cells from adenomas of primary aldosteronism and Cushing's syndrome and an adrenal of nodular hyperplasia of Cushing's syndrome. We compared the data obtained with findings in the case of cultured normal human adrenocortical cells. In the presence of 10(-7) M adrenocorticotropin (ACTH), the addition of either LDL or HDL to the culture medium at a cholesterol concentration of 100 micrograms/ml led to a significant increase in the daily secretion rates of cortisol, dehydroepiandrosterone sulfate (DHEA-S) and aldosterone in the adenoma and nodular hyperplasia cells, as in the normal cells. Although LDL greatly increased the secretion of steroid hormones, no significant difference in steroid secretion following the treatments with LDL and HDL were observed in these cultured cells. The contribution of endogenous cholesterol to steroid production was also high, thereby indicating that the neoplastic transformation did not have untoward effects. Cells from adenomas of primary aldosteronism secreted not only aldosterone, but also cortisol and DHEA-S. The daily secretion rates of these steroids were markedly increased when ACTH was added to the medium. With prolonged exposure to ACTH, however, the rate of aldosterone secretion showed a gradual decrease with the incubation time. This decrease might be due to the impaired conversion of corticosterone to 18-hydroxycorticosterone. In case of adenomas in patients with Cushing's syndrome, the secretion of steroid hormones varied in quantity and quality, depending on the type of plasma cortisol response to the rapid ACTH test in vivo, thereby suggesting that the adrenocortical adenoma of Cushing's syndrome might be divided into two subtypes. These results indicate that human functioning adrenocortical adenoma cells utilize plasma lipoproteins as a source of cholesterol for steroidogenesis during the prolonged stimulation of steroid secretion.     

Serum steroid hormones including 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone in juvenile and adult bonnethead sharks, Sphyrna tiburo.

Previous studies in the placental viviparous bonnethead shark, Sphyrna tiburo, have correlated 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone with reproductive events in both males and females. However, several key reproductive events, including implantation, maintenance of pregnancy, and parturition, did not correlate with these four steroid hormones. Therefore, the present study investigated three steroid hormones, 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone, which have demonstrably important roles in the reproductive cycles of teleosts. It was hypothesized that one or more of these three hormones would correlate with specific reproductive events in S. tiburo. Concurrently, developmental (growth and/or maturation) analyses of these three steroids plus 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone were investigated in juvenile bonnethead sharks. Serum dihydroprogesterone concentrations were highest in mature females and 11-ketotestosterone concentrations were highest in mature males. In mature females, 11-ketoandrostenedione levels were elevated from the time of mating, through six months of sperm storage and another four months of gestation. At parturition concentrations became significantly lower and remained lower until mating occurred again in another two to three months. Serum 11-ketotestosterone concentrations were the highest at implantation though not significant. In mature males, significantly elevated serum levels of dihydroprogesterone occurred in April and May, near the start of annual testicular development. During growth in males, testosterone and dihydrotestosterone increased progressively and in females, testosterone increased progressively. At maturity in males, significant increases occurred in testosterone and 11-ketotestosterone concentrations while, in females, dihydroprogesterone, 11-ketotestosterone, 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone concentrations increased. This study shows that although testosterone may be the primary androgen in the bonnethead shark, other derived androgens may have important functions in growth, maturation, and reproduction. J. Exp. Zool. 284:595-603, 1999.     

Hormonal effects, tolerability, and preliminary kinetics in men of MK-906, a 5 alpha-reductase inhibitor.

The hormonal effects following the acute (single dose) administration of a 4-azasteroid inhibitor of 5 alpha-reductase (MK-906) were evaluated in 10 healthy male volunteers. Marked suppression of serum dihydrotestosterone (DHT) was observed after the administration of single doses as low as 12.5 mg. The mean percent decrease in DHT at 24 hours in the group treated with a single 25-mg dose was 56% +/- 10% compared with the baseline. The suppression of plasma DHT levels continued for up to 72 hours. This study demonstrates that administration of single oral doses (12.5 to 400 mg) of MK-906 results in a significant decrease in the conversion of testosterone to DHT.     

Metabolic effects of low aflatoxin B1 levels on broiler chicks.

The effects of daily ingestion of aflatoxin B1 (AFB1) on growth, feed intake, plasma glucose, plasma cholesterol, plasma amino acids, plasma albumin, plasma ceruloplasmin, muscle amino acids, liver lipid, and bone strength were studied. For 3 weeks, beginning at an age of 2 days, broiler chicks were dosed daily per os with 50 or 100 micrograms of AFB1 per kg of body weight. Body weight and feed consumption were recorded daily, and metabolic responses were determined at 3 weeks. Treatment with AFB1 did not significantly alter body weight or feed intake. Relative liver weight showed a significant increase at the highest dose, with a significant concomitant increase in liver lipid and decrease in hepatic zinc. Relative spleen and heart weights were not affected by the toxin. Plasma glucose and cholesterol were significantly elevated at the highest dose. AFB1 significantly decreased plasma lysine and histidine and significantly increased muscle histidine, arginine, and valine. AFB1 decreased plasma albumin and markedly increased plasma ceruloplasmin. Dimensions of the long bones (femur and tibiotarsus) were not altered by the toxin. However, AFB1 caused a significant linear decline in the resistance of bone to breakage ("bone breaking strength"). The results indicate that low levels of AFB1 reduced bone strength in broiler chicks. The alterations in blood parameters indicated that AFB1 can disrupt metabolism even at low levels.