Effects on Endocrine Function

Cimetidine (for treatment of peptic ulcers) competes with dihydrotestosterone for receptors in the testis and accessory sex glands. The more common sequelae are low sperm count and gynacomastia. Epidemiological evidence has shown that occupation exposure to oral contraceptives can induce gynacomastia in exposed males. Diethylstilbestrol (DES) antagonizes the activity of fetal testosterone. In the male offspring, testicular hypoplasia, abnormal semen parameters, and infertility result. Ketoconazole has be shown to be transported to the seminal fluid and to immobilize the sperm. 

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Effect on endocrine function Catecholamines are important endogenous regulators of hormone secretion from a number of glands. Insulin secretion is stimulated by beta receptors and inhibited by a2-receptors. Similarly, renin secretion is stimulated by Pj and inhibited by receptors indeed, beta-receptor antagonists may lower plasma renin at least part by this mechanism. 

Changes in serum proteins and other effects on endocrine function (see above) must be taken into account when thyroid, adrenal, or pituitary function is being evaluated. Increases in sedimentation rate are thought to be due to increased levels of fibrinogen. 

Mixture Effects on Endocrine Function—Case Studies... 

The plausibility that PCB effects on reproductive function (and other functions such as neurobehavior and immunological competence) may involve PCB effects on endocrine functions has led to investigations of the estrogenic and anti-estrogenic activities of PCB mixtures and individual congeners, and the effects of PCBs or related halogenated aromatic compounds on steroid hormone metabolism via induction of Phase I or Phase n enzymes. How these PCB effects are specifically related to PCB effects on reproductive function is unknown, but the results of these investigations provide further evidence that reproductive effects from PCB mixtures may not be restricted to Ah-receptor mediation alone and are likely to involve multiple mechanisms that have yet to be elucidated. Related information on endocrine disruption is discussed in Section 3.6. 

Various methods can be used to detect toxic effects on endocrine function ... 

In addition to its effect on endocrine function, manganese deficiency can affect pancreatic exocrine... 

NS (chronic) (general population) Endocrine No effect on thyroid function in children 2-77 (levels measured) Siegel et al. 1989 Huseman et al. 1992... 

Goncharova LN, Chirkov W, Rudakova LE. 1984. [Effect of the manufacture of acrylonitrile on endocrine function.] Gig Tr Prof Zabol 23-25. (Russian)... 

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

Oyama T, Taniguchi K, Ishihara H, Matsuki A, Maeda A, Murakawa T, Kudo T. Effects of enflurane anaesthesia and surgery on endocrine function in man. Br J Anaesth 1979 51(2) 141-8. 

In the safety pharmacology protocol, the interaction of multiple endocrine systems in test animals is addressed. As discussed by Harvey (1996) and by Harvey and Everett (2003), effects on adrenocortical function are frequently found in toxicology studies, sometimes related to enzyme induction and effects on steroid biosynthesis (Loose et al. 1983, Nebert and Russell 2002, Weber et al. 1993). Test procedures in animals are required when there is a reason for concern. Frequently however the effects observed are due to stress rather than specific interaction with the target organ, and may involve effects on catecholamine release from the adrenal medulla (Tucker 1996). Recently, much new evidence has been accumulated from the testing of industrial chemicals with effects on adrenal steroid biosynthesis (Harvey and Johnson 2002). 

Gore AC (2001) Environmental toxicant effects on neuroendocrine function. Endocrine 14(2) 235-246. 

Bigsby R, Chapin RE, Daston GP, et al. Evaluating the effects of endocrine disruptors on endocrine function during development. Environ Health Perspect 1999 107 (Suppl 4) 613 18. 

Kamalu, B.P. and Agharanya, J.C., The effect of a nutritionally balanced cassava (Manihot esculenta Crantz) diet on endocrine function using the dog as a model. 2. Thyroid, Br. J. Nutr., 65, 373-379, 1991. 

Other animal models not addressed here, but which have been used to model symptoms of PTSD, include predator stress models. In addition, models of early stress, such as effects of maternal separation on endocrine function, in particular the HPA axis (reviewed in Meaney, 2001), may have implications for the development of stress disorders. Other studies (Cohen et al., 2006) evaluated stress response in juvenile rats as a precursor to adult stress responses. These animal models may help understand the biology of stress, stress vulnerability, and stress resistance and may be useful to identify appropriate therapeutic targets to reduce stress pathology. 

Other effects of PCBs on endocrine function that have been observed in experimental animals include effects on the adrenal glands and serum adrenal steroid levels. 

Other effects of PCBs on endocrine function that have been observed in experimental animals include effects on the adrenal glands and serum adrenal steroid levels (Byrne et al. 1988 Kato et al. 1982a Miller et al. 1993b Rao ad Banerji 1993 Sanders et al. 1974 Wasserman et al. 1973). Studies that have shown depressed levels of adrenal cortical steroids in PCB-exposed animals are also relevant because depressed levels of adrenal steroids have been associated with hypothyroidism in humans (Dluhy 2000). In hypothyroidism, this effect is thought to result from decreases in both secretion and metabolism of adrenal steroids. 

IEH (1999) IEH Assessment on the Ecological Significance of Endocrine Disruption Effects on Reproductive Function and Consequences for Natural Populations (Assessment A4). Leicester MRC Inst. Environment Health. 

Mizinga KM, Thompson FN, Stuedemann JA, Kiser TE, Smith CK, Powell RG. Effect of endophyte infected seed on endocrine function, body weight, and milk production in postpartum beef cows. J Animal Sci 60(suppl 1) 402 (abstr), 1990. 

Brain, P. F. and Nowell, N. W., 1970, The effects of differential grouping on endocrine function of mature male albino mice. Physiol Behav. 5 907-910. 

In this context, the role of adhesion molecules and complement receptors found on macrophages, neutrophils and NK-cells and the role of leukocyte chemotaxis might be of importance and should therefore be investigated. Furthermore, the influence of polysaccharides on endocrine functions (counter irritant effect), on prostaglandin metabolism, or on the NO-mediators have to be taken into consideration. 

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