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At least 127 records · Page 7Linked to original sources

Ewe effect: endocrine and testicular changes in experienced adult and inexperienced young Corriedale rams used for the ram effect.

Changes in LH, FSH, and testosterone concentrations, testicular firmness and resilience, and scrotal circumference were monitored in 16 Corriedale rams (8 experienced adult and 8 inexperienced young) for 20 days during which they were used to stimulate ewes. The experiment was conducted during November (mid-non-breeding season). Increases (P<0.05) were observed in LH and testosterone concentrations and in testicular firmness and resilience during the first 4 days when rams were in permanent contact with estrual ewes. During the following 13 days, when rams were in contact with non-estrual ewes (i.e. initially estrual ewes were no longer in estrus), LH and testosterone concentrations decreased. When initially anestrous ewes exhibited estrus 17 to 20 days later, concentrations of testosterone increased. Testicular firmness and resilience remained high throughout the period. We conclude that: (1) rams used to stimulate anestrous ewes show an increase in LH and testosterone concentrations beginning at 12 h after joining, and greater concentrations are maintained while estrual ewes and mating are allowed; and (2) estrous and mating activity are probably the most important stimuli for the increase in hormone concentrations.

Animals↗

Hepatic enzyme induction and acute endocrine effects of 2,2',3,3',4,6'-hexachlorobiphenyl and 2,2',3,4',5',6-hexachlorobiphenyl in prepubertal female rats.

Polychlorinated biphenyls (PCBs) with the liable 2,3,6-substitution are important components of certain commercial mixtures and frequently detected in biota, but little is known about their enzyme induction abilities and possible endocrine-disrupting effects. CB 132 (2,2',3,3',4,6'-hexachlorophenyl) and CB 149 (2,2'3,4',5',6-hexachlorophenyl) were investigated in weanling female rats dosed intraperitoneally on days 21 and 22 and killed on day 24 of age. Uterotropic response, serum thyroid hormone, and hepatic enzyme induction were examined in prepubertal female rats treated with these two environmentally relevant 2,3,6-substituted chlorobiphenyl (CB) congeners from 8 mg/kg to 96 mg/kg. The readily metabolized CB 132 did not cause any significant increase in all endpoints measured in the present study. On the other hand, CB 149 was a weak PROD and BROD inducer and a modest depleter of serum thyroxine in prepubertal female rats. The finding of thyroid hormone disruption by CB 149 may lead to biologically significant neurobehavioral and neurochemical changes in developing animals via milk lactation.

Animals↗

Hemodynamic and endocrine effects of acute and chronic administration of nifedipine.

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency towards an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.

Aldosterone↗

Hemodynamic and endocrine effects of acute and chronic administration of nifedipine.

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency toward an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.

Adult↗

Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet.

Leptin produced by adipocytes controls body weight by restraining food intake and enhancing energy expenditure at the hypothalamic level. The diet-induced increase in fat mass is associated with the presence of elevated circulating leptin levels, suggesting the development of resistance to its anorectic effect. Rats, like humans, show different susceptibility to diet-induced obesity. The aim of the present study was to compare the degree of leptin resistance in obesity-prone (OP) vs obesity-resistant (OR) rats on a moderate high-fat (HF) diet and to establish if the effects of leptin on hypothalamo-pituitary endocrine functions were preserved. Starting from 6 weeks after birth, male Sprague-Dawley rats were fed on either a commercial HF diet (fat content: 20% of total calorie intake) or a standard pellet chow (CONT diet, fat content: 3%). After 12 weeks of diet, rats fed on HF diet were significantly heavier than rats fed on CONT diet. Animals fed on HF diet were ranked according to body weight; the two tails of the distribution were called OP and OR rats respectively. A polyethylene cannula was implanted into the right ventricle of rats 1 week before central leptin administration. After 12 weeks of HF feeding, both OR and OP rats were resistant to central leptin administration (10 mug, i.c.v.) (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 62 [50; 78]; OR, 93 [66; 118]; OP, 90 [70; 120] as medians and 95% confidence intervals (CIs) of six rats for each group). Conversely, after 32 weeks of diet both OR and OP rats were partially responsive to 10 mug leptin i.c.v. as compared with CONT rats (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 60 [50; 67]; OR, 65 [50; 80]; OP, 80 [60; 98] as medians and 95% CIs of six rats for each group); the decrease of food intake following 200 mug leptin i.p. administration was similar in all the three groups (calorie intake as a percent of vehicle-treated rats: 86 [80; 92] as median and 95% CI). The long-term intake of HF diet caused hyperleptinemia, hyperinsulinemia and higher plasma glucose levels in OP rats as compared with CONT rats. Plasma thyroxine (T4) was lower in all the rats fed the HF diet as compared with CONT. i.c.v. administration of leptin after 32 weeks of diet restored normal insulin levels in OP rats. Moreover, leptin increased plasma T4 concentration and strongly enhanced GH mRNA expression in the pituitary of OP as well as OR rats (180+/-10% vs vehicle-treated rats). In conclusion, long-term intake of HF diet induced a partial central resistance to the anorectic effect of leptin in both lean and fat animals; the neuroendocrine effects of leptin on T4 and GH were preserved.

Animals↗

Behavioral and endocrine effects of growth hormone administration in aged female rats.

Growth hormone (GH) secretion declines during normal aging along with reproductive activity in mammalian species. Various behavioral changes also occur in aged animals. In these experiments we have studied the effects of GH administration on behavioral and endocrine alterations exhibited by aged (18 months old) female rats of the Sprague-Dawley strain. Animals were selected showing at least 2 weeks of cornified vaginal smears (constant estrous) and treated with GH (0.1 mg/kg SC) daily for 8 weeks. Vaginal smears performed during the drug treatment revealed a recovery of estrous cycle in 60% of animals. GH treatment was also followed by an increased acquisition of shuttle-box active avoidance behavior and a facilitated retention of passive avoidance response. Compared to saline-injected controls, female rats treated with GH also exhibited a decrease of novelty-induced excessive grooming. The endocrine pattern of GH-treated aged female rats revealed a decrease in plasma prolactin levels and an increase in luteinizing hormone and 17 beta-estradiol levels as compared to those of control animals. These results support the concept that behavioral and endocrine alterations occurring in aging are not irreversible and that GH may interfere with these changes probably by means of its trophic action on different target organs.

Aging↗

Long-term immune-endocrine effects of bereavement: relationships with anxiety levels and mood.

Psychological, endocrine and immune parameters were measured over a 6-month period in 14 healthy subjects who underwent an unpredictable acute emotional stress (e.g. sudden death of a loved one) compared with 14 controls who did not. Probands were profoundly stressed as assessed 10 days after bereavement by their scores on the Hamilton Rating Scales of Anxiety and Depression, adrenocorticotropin and cortisol plasma concentrations, and non-suppression in response to dexamethasone. Functional alterations of immune parameters, such as responsiveness of peripheral blood lymphocytes to mitogens, were found 40 days after bereavement. Despite a normal number of circulating lymphocyte subsets, the functional activity of natural killer (NK) cells was markedly reduced at day 40. Changes in the intracellular concentration of beta-endorphin in peripheral blood mononuclear cells correlated with anxiety and depression scores. Controls showed no changes in psychometric, endocrine and immune measures during the 6-month study. Cluster analysis revealed two groups of bereaved subjects with different patterns of immune and endocrine changes: (1) Five subjects, characterized by harm-avoidant temperament and long-lasting dysphoric mood, showed reduced responsiveness of peripheral blood lymphocytes to mitogens, decreased NK cell activity and non-suppression in response to dexamethasone that persisted for 6 months. (2) Nine subjects showed significant changes only during the early phase after bereavement. Our data suggest that the immunological consequences of stress do not simply overlap with psychological and endocrine alterations, and are particularly severe and long-lasting in a subgroup of subjects, indicating the importance of individual variability in the capacity to cope with stress.

Adaptation, Psychological↗

Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale.

OBJECTIVES: Angiotensin II (ANG II) is known to be a potent vasoconstrictor agent in the pulmonary circulation. Furthermore, type 1 ANG II receptor blockade with losartan attenuates acute hypoxic pulmonary vasoconstriction in normal subjects. The aim of this study was therefore to evaluate the haemodynamic and endocrine sequelae of type 1 ANG II receptor blockade in patients with hypoxaemic cor pulmonale. METHODS: Nine patients with chronic obstructive pulmonary disease (COPD) age 67 +/- 3 years with pulmonary hypertension and normal left ventricular systolic function were studied on two separate occasions in a double-blind, placebo-controlled, crossover study. They were randomised to receive either 50 mg of oral losartan or matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Haemodynamic measurements and venous blood samples were taken at baseline and after 2 and 4 h. RESULTS: Maximal effects were observed at 4 h where losartan compared to placebo resulted in a significant reduction in both MPAP (28.6 +/- 2.0 vs 32.4 +/- 1.5 mmHg) and TPR (428 +/- 40 vs 510 +/- dyn.s.cm-5), respectively. Similarly losartan compared to placebo resulted in a significant reduction in MAP (87 +/- 4.5 vs 93 +/- 3.2 mmHg) and SVR (1293 +/- 94 vs 1462 +/- 112 dyn.s.cm-5), and significantly increased CO (5.58 +/- 0.43 vs 5.31 +/- 0.42 l/min). In addition, plasma aldosterone was significantly lower after treatment with losartan compared to placebo: 76 +/- 23 vs 164 +/- 43 pg/ml respectively. CONCLUSIONS: Thus, selective type 1 ANG II receptor blockade appears to have beneficial pulmonary and endocrine effects, suggesting a possible therapeutic role in the management of hypoxaemic cor pulmonale.

Aged↗

Endocrine effects in the hazard assessment of drugs used in animal production.

Criteria of toxicological assessment are currently reviewed to ensure an adequate protection to susceptible groups, such as infants and children; in particular, concern arises about altered endocrine homeostasis in the developing organism, eliciting possible persistent effects such as reproductive disturbances and increased risk of tumours in target organs. Such items are obviously relevant also for veterinary drugs, whose main safety issue is potential lifetime exposure to residues. Two groups of chemicals, nitroimidazoles and imidazole antifungals, are reviewed as examples of the relevance of endocrine toxicity to the hazard assessment of compounds used in animal production. Nitroimidazoles are metabolized into genotoxic intermediates; in rodents they induce testicular toxicity and carcinogenicity. In particular, mammary neoplasms, mostly fibroadenomas, are consistently induced in rats as the most important effect in chronic studies; this may hint to possible endocrine-related mechanisms. Accordingly, evidences on other chemicals (e.g., triazines) show mammary tumorigenicity in rodents associated to hormonal alterations. In fact, nitroimidazoles affect synthesis of both pituitary and steroid hormones in vitro and rise progesterone and FSH levels in rats; also, limited clinical data in humans indicate endocrine-related effects. Overall, nitroimidazoles appear to affect the endocrine balance; however, the actual importance of such alterations, especially in regards to rat mammary tumours, has yet to be clarified. Imidazole antimycotics are broad-spectrum inhibitors of steroid synthesis; accordingly, diverse reproductive and developmental alterations are observed, depending on age and sex of animals exposed. Effects include pregnancy loss, delayed pup growth as well as reduced weight of androgen-dependent tissue; however, it is still difficult to identify the most susceptible biological phase. Overall the potential for inducing endocrine-related alterations should be carefully evaluated also for drugs used in animal production. A screening battery should produce a distinct fingerprint for each major endocrine activity, thus targeting longer-term tests (such as the two-generation study) on the most relevant endpoints. Moreover, the validation of molecular approaches would contribute to a biologically-based evaluation, by providing insights on such items as early effects and species-specificity.

Animal Experimentation↗

Early metabolic and endocrine effects of perorally administered beta-adrenoceptor agonists in calves.

Early metabolic and endocrine changes in calves in response to two beta-adrenoceptor agonists in the absence and presence of the beta-adrenoceptor blocking agent propranolol have been studied in calves. The agonists were administered p.o. with milk in different amounts, whereas propranolol was infused i.v. for 10 h. Respiration volume, O2 consumption, CO2 production, respiratory quotient, blood glucose, lactate, non-esterified fatty acids and insulin transiently increased within 2-4 h in a dose-dependent manner, whereas glucagon, adrenaline, noradrenaline, triiodothyronine, urea, albumin and protein did not change significantly. Propranolol completely inhibited the effects on glucose, lactate, non-esterified fatty acids and insulin. Six hours after the administration of the beta-adrenoceptor agonists, the glucose clearance rates following i.v. infusion of glucose were markedly reduced and the glucose decrements in response to an i.v. injection of insulin were much smaller than in the absence of the beta-adrenoceptor agonists. The metabolic changes demonstrate an enhanced glycogenolysis and fat mobilisation, an increased metabolic rate and the development of insulin resistance within 6 h after the administration of the beta-adrenoceptor agonists.

Administration, Oral↗

Endocrine effect of a methionine-enkephalin derivative (FK 33-824) in man.

The endocrine profile of FK 33-824, 0.5 mg i.m., was determined in comparison with placebo or pretreatment with naloxone, 4 mg i.v., in 14 healthy men. Prolactin (PRL), growth hormone (GH), ACTH, cortisol, gonadotropins (LH, FSH), thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), insulin and glucagon were measured and free water clearance was calculated from urine volumes and osmolar clearances. FK 33-824 increased PRL and GH (p less than 0.001). ACTH was below assay sensitivity but cortisol was significantly lowered (p less than 0.001). Free water clearance was enhanced (p less than 0.01) and the remaining parameters were unchanged. Naloxone alone had no hormonal effect but abolished the increase in PRL and GH following injection of FK 33-824 without modifying the decrease in plasma cortisol or the increase in free water clearance following the same treatment. The results indicate that the effect of FK 33-824 on PRL and GH release is mediated by opiate receptors. Other mechanisms or naloxone nonsensitive receptors may be implicated in the effects recorded on cortisol and FWC.

Adrenocorticotropic Hormone↗

Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women.

Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.

Adult↗

Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior.

OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. RESULTS: Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.

Acne Vulgaris↗