The endocrine system

Interaction of vitamin D and its metaboUtes with sex hormones has been demonstrated, particularly ia birds ia which the egg-laying functions combine calcium needs and reproductive activity. The metaboUtes of vitamin D behave as hormones. As such, they play an active role ia the endocrine system, along with other hormones, to maintain the various body functions. Several biological influences of metaboUtes of vitamin D have been studied, including effects related to cancer (193—197), skin diseases (198—201), immunomodulatory effects (202,203), and Alzheimer s disease (204—206) (Fig. 9). 

A second problem concerns delimiting the mechanisms of action which should be included in the definition, to exclude effects which are a secondary consequence of overt toxicity in other body systems. For example, disruption to the endocrine system caused by general metabolic disturbance, such as in severe liver damage, should not be grounds for calling a chemical an ED. 

There are many possible mechanisms by which chemicals may interact with the endocrine system, some of which are discussed below. 

Many different test systems have been used to investigate the ability of chemicals to interact with components of the endocrine system. The usefulness and applicability of the available methods has been the subject of much debate. Four key texts are particularly helpful in reviewing and giving guidance on currently available test methods and strategies for testing EDs. ... 

Tier 2 is intended to determine and characterize the effects of the chemical on the endocrine system and includes ... 

Figure 1 A schematic diagram of the endocrine system of fish. TRH = thyrotrophin releasing hormone GnRH = gonadotrophin releasing hormone CRH = corticotrophin releasing hormone TSH = thyroid stimulating hormone GtH = gonadotrophins I and II ...

The liver plays an important role in the endocrine system. The concentrations of hormones in plasma, and the activity of the glands which secrete them, are determined by the rate at which they are deactivated by the liver. The liver also has a major function in female reproduction since it is the target tissue of ovarian estrogen, to which it responds by producing the yolk protein vitellogenin. " Xenobiotics that affect either of these functions can therefore be considered to be potential endocrine disrupters. 

Capen, C. C. (1996). Toxic responses of the endocrine system. Jn Casarett and DouU s Toxicology The Baste Science, of Poisons (C. D. Klaassen, Ed. , pp. 617-640. McGraw-Hill, New York. 

UNIT IX Drugs That Affect the Endocrine System... 

Unit IX discusses drugp that affect the endocrine system and consists of five chapters antidiabetic drugs, pituitary and andrenocortical hormones, thyroid and antitliyroid drag s, male and female hormones, and dragp acting on the uterus. 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine system because of the abihty of these chemicals to mimic or block endogenous hormones, or otherwise interfere with the normal function of the endocrine system. Chemicals with this type of activity are most commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995 Livingston 1978 Mayr et al. 1992). 

Some biomarkers only provide a measure of exposure others also provide a measure of toxic effect. Biomarkers of the latter kind are of particular interest and importance and will be referred to as mechanistic biomarkers in the present text. Some mechanistic biomarker assays directly measure effects at the site of action as described in Section 2.4 (see Chapter 4, Table 4.2, for examples). Inhibition of acetylcholinesterase is one example. Others measure secondary effects on the operation of nerves or the endocrine system (examples given in Table 4.2 and Chapters 15 and 16). 

---