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Central effects of tricyclic compounds on the endocrine system--an in vitro study.

The present study involves the effects on corticotropin (ACTH) release of neuro- and thymoleptic tricyclic antidepressant compounds (TrcACs: chlorpromazine, promethazine, haloperidol, imipramine, amitriptyline) and their interactions with lysine-8-vasopressin (LVP) and corticosterone (B). As an in vitro model, 14-day monolayer pituitary cell cultures of Wistar rats were employed. The ACTH concentrations of the supernatant media were measured by radioimmunoassay. TrcACs augmented ACTH release; their combination with LVP, however, did not result in further stimulation; moreover, when combined with TrcACs + LVP, B did not inhibit, but rather paradoxically increased their ACTH-releasing action. As none of these phenomena were followed by relevant changes in intracellular cyclic adenosine monophosphate content, the mechanism of action may be proposed to involve a protein kinase C route.

Adrenocorticotropic Hormone↗

Effect on the endocrine system of a new dopaminergic agent, ibopamine.

Ibopamine, an oral dopaminergic and adrenergic agent, was given to 19 healthy men to investigate the effect of this dopamine analogue on carbohydrate metabolism. In a three-part study six subjects received ibopamine alone, seven subjects were pretreated with metoclopramide (a dopamine antagonist), and six subjects received phentolamine (an alpha-receptor antagonist) and propranolol (a beta-receptor antagonist) to study the specific mechanisms involved. In these single-blind, controlled, randomized studies, effects on fasting glucose, insulin, glucagon, and prolactin were evaluated. Ibopamine, 300 mg, produced a statistically significant increase in fasting glucose and insulin levels but had no effect on glucagon or prolactin levels. Pretreatment with metoclopramide or phentolamine did not block these effects, but pretreatment with propranolol significantly (P less than 0.05) blunted the increase in fasting glucose and insulin levels. These findings indicate that, unlike other dopaminergic agonists, administration of ibopamine results in increased glucose levels without affecting glucagon. The effect on glucose is mediated through stimulation of beta-adrenergic receptors.

Adult↗

Hypothesis: etiology of atherosclerosis and osteoporosis: are imbalances in the calciferol endocrine system implicated?

Atherosclerosis and osteoporosis are currently considered unrelated diseases. Osteoporosis involves bone calcium (Ca) loss and predominantly affects females after menopause. Atherosclerosis is an illness predominantly affecting males, and is primarily characterized by abnormal lipid metabolism. However, pathological calcification of the arterial wall is an underlying feature of atherosclerosis. Ca homeostasis is thus important in atherosclerosis as well as in osteoporosis. Men also develop osteoporosis although at a later age than women, and, as osteoporosis progresses in women, there is an accompanying calcification of arteries leading to increased incidence of atherosclerosis in aging women. Thus, during old age, both atherosclerosis and osteoporosis are prevalent in both males and females. The dramatic increase in atherosclerosis among women as they develop osteoporosis suggests that the two illnesses may be more closely related than previously realized. The use of vitamin D as a food supplement coincides with epidemic onsets of atherosclerosis and osteoporosis, and excess vitamin D induces both conditions in humans and laboratory animals. These observations suggest a role for chronic vitamin D excess in the etiology of the two illnesses. Magnesium (Mg) deficiency, nicotine, and high dietary cholesterol are contributing factors that accentuate adverse effects of vitamin D.

Animals↗

Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system.

The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of 203Pb and 47Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] as their only source of the vitamin, the absorption of both 47Ca and 203Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in 47Ca and 203Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)2D3, the intestinal absorption of 47Ca and of 203Pb was increased, as well as the intestinal CaBP levels. Intracardial injection of increasing doses of 1,25(OH)2D3 to rachitic chicks resulted in a concomitant increase in 203Pb absorption in a manner that correlated with the degree of synthesis of CaBP. Ingestion of lead by the chicks was found to impair growth and renal production of 1,25(OH)2D3, resulting in lowered circulating and intestinal content of the hydroxylated metabolites of cholecalciferol.

Animals↗

Sleep and the endocrine system: new associations to old diseases.

Sleep and sleep disorders play a prominent role in hormone regulation. Given that sleep disordered breathing (SDB) and diabetes mellitus (DM) are thought to result from obesity, it has been assumed that when the two coexist, the diabetes was caused by the obesity. However, new data has shed light on the effects that SDB, sleep deprivation, and snoring have on glucose regulation. It now appears that in addition to causing daytime drowsiness, cardiovascular disease, mood and memory disturbances, impotence, and car wrecks, obstructive sleep apnea (OSA) also promotes insulin resistance. Though data is still sketchy on the optimum management of coexisting DM and OSA, large-scale studies will most likely prove that homeostatic glucose control in patients with sleep apnea will require aggressive treatment of their SDB.

Diabetes Mellitus, Type 2↗

Effects on the endocrine system of long-term treatment with the non-steroidal anti-androgen Casodex in patients with benign prostatic hyperplasia.

OBJECTIVE: To study the hormonal changes resulting from long-term use of the non-steroidal anti-androgen Casodex. PATIENTS AND METHODS: A randomized, placebo-controlled study was carried out on 27 patients with benign prostatic hyperplasia (BPH). Fourteen patients received Casodex 50 mg daily for 24 weeks and 13 received a placebo. The patients were followed up for a further 24-week period. RESULTS: Serum concentrations of luteinizing hormone (LH) increased by an average of 40% while follicle-stimulating hormone (FSH) remained unchanged. Testosterone increased by 35%, oestradiol by 29% and oestrone by 23%; all changes were statistically significant. Levels of androstenedione and dihydrotestosterone increased by 11% and 15%, respectively, but these increases did not reach statistical significance. A non-significant increase was also observed for sex hormone-binding globulin. The hormonal changes were reversible upon discontinuation of therapy. Prolactin and dehydroepiandrosterone-sulphate levels did not change. CONCLUSION: This study indicates that Casodex, due to competitive inhibition of central androgen receptors, increases LH secretion, thus causing increased production and increased metabolism of testosterone.

Aged↗

Effects of ketanserin on cardiovascular, sympatho-adrenal and endocrine systems during physical exercise in man.

Blood pressure, heart rate, oxygen consumption, plasma concentrations of catecholamines, renin, aldosterone and lactate were measured in 6 normotensive volunteers during a randomized cross-over study of oral ketanserin (20 mg X 7) and placebo; measurements were made at rest and during maximal dynamic exercise on a bicycle ergometer. At rest ketanserin reduced blood pressure without modifying heart rate or plasma noradrenaline and adrenaline. Duration of exercise and blood lactate levels did not differ between the ketanserin and the control group. During exercise only systolic blood pressure was significantly decreased on ketanserin at maximal work rate whereas heart rate did not change. Plasma noradrenaline was significantly increased and plasma aldosterone significantly decreased during exercise in ketanserin-treated subjects whereas plasma renin activity and plasma adrenaline remained unchanged. Finally, under ketanserin oxygen consumption during exercise was reduced. The results suggest that ketanserin might interfere with the sympathetic nervous system and aldosterone secretion in man.

Adrenal Glands↗