Hormonal level, effect

Darnerud, P.O., Morse, D.C., Klasson-Wehler, E. et al. (1996). Binding of 3,3, 4,4 TCB metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice. Toxicology 106, 105-114. 

Kilic-Okman T, Kucuk M, Altaner S (2003) Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. FertilSteril 80 1330-1332... 

To understand the MOA by which the thyroid tumors are produced, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels, and hepatic thyroxine UDP-glucuronosyltransferase activity was also investigated [128]. The treatment of male rats with 8,000 ppm pyrethrins, female rats with 3,000 and 8,000 ppm pyrethrins, and both sexes with phenobarbital resulted in increased thyroid gland... 

Radiation, of course, affects specific chemical substances present in biological systems. It appears evident that when the enzymic and hormonal levels of two individuals differ markedly in pattern by inheritance, there will be corresponding differences (as there are in mice) to radiation effects. 

In the ebb phase, there is increased activity of the sympathetic nervous system and increased plasma levels of adrenaline and glucocorticoids but a decreased level of insulin. This results in mobilisation of glycogen in the liver and triacylglycerol in adipose tissue, so that the levels of two major fuels in the blood, glucose and long-chain fatty acids, are increased. This is, effectively, the stress response to trauma. These changes continue and are extended into the flow phase as the immune cells are activated and secrete the proinflammatory cytokines that further stimulate the mobilisation of fuel stores (Table 18.2). Thus the sequence is trauma increased endocrine hormone levels increased immune response increased levels of cytokines metabolic responses. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

A nonlinear approach should be selected when there are sufficient data to ascertain the mode of action and to conclude that it is not linear at low doses, and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses. The POD is in this case generally a BMDL when incidence data are modeled. A sufficient basis to support this nonlinear procedure is likely to include data on responses that are key events in the carcinogenic process. This means that the POD may be based on these precursor response data, for example hormone levels or mitogenic effects, rather than tumor incidence data. A nonlinear approach can be used to develop an RfD or an RfC. This approach expands such reference values, previously reserved for threshold effects, to include carcinogenic effects determined to have a nonlinear mode of action. A nonlinear approach should generally not be used in cases where the mode of action has not been ascertained. 

The authors concluded that the mixture induced effects on the liver and the kidney, and on the general metabolism at high doses but caused only minor effects on immune function, reproductive hormone levels, or general indices of reproductive function measures. The results suggested that additive or synergistic effects of exposure to contaminants resulting in residue levels representative of contemporary human tissue levels are unlikely to result in adverse effects on immune function or reproductive physiology in male rats. 

Fibrocystic breast disease Danazol is usually effective in decreasing nodularity, pain, and tenderness, but it alters hormone levels recurrence of symptoms is very common after cessation of therapy. 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Treatment-related altered serum th5Toid hormone levels indicate that chlorine dioxide and chlorite may exert toxic effects that are mediated through the neuroendocrine axis. Changes in thyroid hormones have been reported in laboratory animals that were either directly exposed to chlorine dioxide (repeated doses as low as 9 mg/kg/day), or exposed to chlorine dioxide or chlorite via their mothers (maternal doses of chlorine dioxide and chlorite as low as 13 and 9 mg/kg/day, respectively) during pre- and postpartum development (Bercz et al. 1982 Carlton and Smith 1985 Carlton et al. 1987, 1991 Mobley et al. 1990 Orme et al. 1985). 

The onset of effect of these drugs is slow 2-A weeks is required before stored hormons are depleted and clinical signs of improvement are observed. Short-term treatment is indicated to prepare patients for surgery or radioiodine therapy, while long-term treatment is indicated for cases inappropriate for surgery or radioactive modalities or where medical therapy alone is used. Usually the patient is advised to continue treatment for 1-2 years spontaneous remission occurs in about 50% of cases treated in this way. There is no way to predict remission confidently, however hormone levels, TSAb titer, and goitre size are useful guides. 

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