Other Hormonal Effects

Although it is generally recognized that the thyroid secretions exert a profound effect on carbohydrate metabolism in animal tissues, no clear-cut evidence is available which would implicate a member of the glycolytic system in the chain of events by which the hormone exerts its effect on the organism. 

In all body fluids a relatively constant amount of cations and anions must be maintained by the cell for it to function normally. Since any disturbance in the ratio of ionic species in the tissue may stimulate profound changes, a consideration of these effects in terms of the known enzymes systems of the glycolytic cycle would be of considerable value. 

At present the knowledge in this field is of a rather descriptive nature in so far as the monovalent and divalent cations and anions are concerned. In the near future these effects will undoubtedly be described in physical-chemical terms. 

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As with other hormone effects, steroid hormones act by attaching to a protein receptor molecule. The fact that such small chemical differences among these basically very similar steroid molecules can result in such profoimdly different effects is just another indication of the extraordinary power of selective molecular recognition by protein molecules. Unlike the receptors for many other hormones, receptors for steroid hormones are not embedded in the cell membrane. They do not need to be because these hormone molecules are both small and hydrophobic... 

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). 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

The possible mechanism kidney-induced hypertension is discussed in Section 2.4.2, Mechanisms of Toxicity. Lead appears to affect vitamin D metabolism in renal tubule cells, such that circulating levels of the vitamin D hormone, 1,25-dihydroxyvitamin D, are reduced. This effect is discussed later in this section under Other Systemic Effects. 

DHEA is an adrenal hormone that is a precursor to the sex hormones testosterone and estrogen, as well as other hormones. DHEA is reported to increase testosterone and decrease total body fat, and also to have anabolic and anti-aging effects. The... 

Table 11.1 Some metabolic effects of insulin. These effects are generally countered by other hormones (glucagon and, in some cases, adrenaline). Hence, the overall effect noted often reflects the relative rates of these hormones present in the plasma...

The progestin-only Minipills tend to be less effective than combination OCs, and they are associated with irregular and unpredictable menstrual bleeding. They must be taken every day of the menstrual cycle at approximately the same time of day to maintain contraceptive efficacy. They are associated with more ectopic pregnancies than other hormonal contraceptives. 

The mechanism by which insulin impairs renal calcium reabsorption is still under investigation, but some progress has been made toward revealing that the insulin effect is directly on the renal tissues, rather than an indirect effect on other hormones or metabolites. 

In some situations, one might also envisage analyses of other combinations of specific tumors, such as tumors at related sites (e.g., endocrine organs if the compound had a hormonal effect) or of similar histological type. 

Other Systemic Effects. Adrenal fibrosis with lipid accumulation was reported in one study in mice, but these effects have not been observed in humans known to be exposed to heptachlor and have not been verified in other species. There has been no measurement of adrenal hormone in exposed humans or animals. Body weight changes have, in general, been accompanied by a decrease in food consumption, due possibly to taste aversion. 

Other hormones Thyroxine has long been known to increase metabolic rate, although the mechanism for this effect is not totally clear (Silvestri et al. 2005). More recently the hormone leptin, which is secreted by adipose tissue, has also been found to increase the metabolic rate. This effect of leptin is considered to play a role in controlling the amount of adipose tissue in the body, although this is a controversial subject (Chapter 12). 

Cilest is a combined hormonal contraceptive that contains ethinylestradiol and norgestimate. These products may cause nausea, especially on commencement of therapy. Other side-effects that may occur in decreasing order of probability include fluid retention, reduced menstrual loss and photosensitivity. Acne is not commonly associated with combined hormonal contraceptive. Hormone therapy consisting of ethinylestradiol and cyproterone may be used for the management acne in women. 

As discussed on p. 244, the hormone receptor does not interact directly with the RNA polymerase, but rather—along with other transcription factors—with a coactivator/me-diator complex that processes all of the signals and passes them on to the polymerase. In this way, hormonal effects lead within a period of minutes to hours to altered levels of mRNAs for key proteins in cellular processes ( cellular response ). 

Although cytokines rarely show structural homologies with each other, their effects are often very similar. The cytokines differ from hormones (see p. 370) only in certain respects they are released by many different cells, rather than being secreted by defined glands, and they regulate a wider variety of target cells than the hormones. 

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