The effects of hormones

Sodium transport across amphibian epithelia (and kidney epithelia, too) can be increased by two hormones, antidiuretic hormone and aldosterone. Antidiuretic hormone (AOH) also increases water permeability in these situations and this is. 

The effects of hormones therefore, override the cellular homeostatic mechanisms for the sake of homeostasis for the organism as a whole. In the previous section, it was noted that the entry step for sodium was the rate determinant of the level of sodium transport which can be maintained by the epithelia. There is a large amount of evidence, which cannot be reviewed here, to suggest that both of the hormones which increase sodium transport do so by modifying the entry step that is, they increase sodium permeability. 

The effects of aldosterone are different. First, the onset of its effect takes at least one hour, while ADH takes only a few minutes. Aldosterone causes an increase in the density of channels [196,201,203] with no change in apparent affinity to amiloride. Thus, as far as the probe molecule is concerned, the new channels appear to be identical to the pre-existing channels. The effect of aldosterone on channel density is blocked by inhibitors of transcription and translation [196], indicating that de novo protein synthesis is involved in the effect. Whether the new protein is actually new channel or whether the new protein can expose pre-existing but occluded sites in the membrane has not been answered. 

The turnover of sodium channels in epithelial membranes is slow. After inhibition of protein synthesis, the half-time for the disappearance of the channels is approximately 60 h [204]. 

The complexity of the changes of amiloride-binding site density, and hence presumably of sodium channels, which can take place in these epithelia are only just beginning to be understood. It is not surprising, therefore, that the ideal diuretic has not been found, for any perturbation at one part of the nephron is likely to affect the ambient sodium concentration at a distal part. The ensuing adaptive changes, plus the influence of hormones, are such as to produce complex patterns of excretion. 

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Membrane asymmetries in the transverse direction (from one side of the membrane to the other) can be anticipated when one considers that many properties of a membrane depend upon its two-sided nature. Properties that are a consequence of membrane sidedness include membrane transport, which is driven in one direction only, the effects of hormones at the outsides of cells, and the immunological reactions that occur between cells (necessarily involving only the outside surfaces of the cells). One would surmise that the proteins involved in these and other interactions must be arranged asymmetrically in the membrane. 

As noted above, many of the AEDs induce hepatic microsomal enzyme systems and thus reduce the effectiveness of hormonal contraceptives. Women taking AEDs that may reduce the effectiveness of hormonal contraceptives should be encouraged to also use other forms of birth control. Due to induction or inhibition of sex hormone metabolism and changes in binding of hormones to sex hormone binding globulin, some AEDs may reduce fertility. For example, valproate has been associated with a drug-induced polycystic ovarian syndrome. Women who experience difficulties with fertility should seek the advice of health care professionals with expertise in fertility. 

For example, a single hormone-activated gene induces the formation of many mRNA molecules and each mRNA molecule may be used to synthesize many enzyme molecules. Furthermore, the effects of hormones using this mechanism are prolonged. As long as the newly synthesized enzyme is active, the effect of the initiating hormone persists. 

Garcfa-Martfnez MC, Labios M, Hermenegildo C, Tarfn JJ, O Connor E, Cano A (2004) The effect of hormone replacement therapy on Ca2+ mobilization and P-selectin (CD62P) expression in platelets examined under flow cytometry. Blood Coagul Fibrinolysis 15 1-8... 

Walsh BW, Cox DA, Sashegyi A, Dean RA, Tracy RP, Anderson PW (2001) Role of tumor necrosis factor-alpha and interleukin-6 in the effects of hormone replacement... 

Walsh BW, Paul S, Wild RA, Dean RA, Tracy RP, Cox DA, Anderson PW (2000) The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women a randomized, controlled trial. J Clin Endocrinol Metab 85 214-218... 

An account of the principles which help to understand how hormones achieve their roles in the body is given in Chapter 12. The understanding is based on separation of the effects of hormones into three components the action, the effects (biochemical and physiological) and the function. A steroid hormone binds to a cytosolic intracellular receptor, which then moves into the nucleus where it binds to DNA at a specific site (the steroid response element) and activates genes which result in the formation of proteins that elicit biochemical and physiological effects. This is discussed for cortisol in Chapter 12 and aldosterone in Chapter 22. Much of the interest in the reproductive steroid hormones is in the physiological effects and how these account for their functions. 

Chao HM, Spencer RL, Frankfurt M, et al The effects of hormone manipulation on amyloid precursor protein APP695 mRNA expression in the rat hippocampus. J Neuroendocrinol 6 517-521, 1994... 

Gorski JC, Wang Z, Haehner-Daniels BD, Wrighton SA, Hall SD. The effect of hormone replacement therapy on CYP3A activity. Clin Pharmacol Therapeut 2000 68(4) 412-A17. 

Hormonal control of mating behaviour is well documented in animals. In rats, estrogen and, to a lesser extent, progesterone control lordosis behaviour via the central nervous system (CNS). In female non-human primates, attractiveness and proceptivity change during the menstrual cycle or as a result of sex steroid administration. The effects of hormones on receptivity are unclear. It is assumed that steroid hormones influence behaviour in humans as they do in animals however, it is difficult to differentiate the effects of social and other environmental factors from the effects of sex steroids on mating behaviour in humans. 

Fast metabolic adjustments (on the time scale of seconds or less) at the intracellular level are generally allosteric. The effects of hormones and growth factors are generally slower (seconds to hours) and are commonly achieved by covalent modification or changes in enzyme synthesis. 

Combinations of oestrogens and androgens have been shown to result in greater growth responses than either agent alone. The effect of hormones on the growth and body composition of animals has recently been reviewed (81MI10811). 

Another approach to the study of the effects of hormone replacement therapy on the breast is to examine breast density, using mammography and the Wolfe classification. In a randomized study of 166 menopausal women, using this technique, there was increased breast density after 6 months of treatment eight times more commonly in those who took estradiol and norethisterone acetate than in those who took tibolone (186). The significance of this increased density is not clear, but it should for the present be regarded as undesirable,... 

This is one of the newer drugs appearing on the bodybuilding scene that I would like to comment only briefly on. The human body produces several growth factors that are mediators and intermediates. In short this means they translate or decrease/increase the effect of hormones and other growth factors. 

Selevan et al., 2000). This has been worked out in some detail for certain systems and agents (e.g. central nervous system development and radiation exposure) in most cases, however, the exact time when organ systems are susceptible to the actions of toxic chemicals is unknown. Limited data are available on susceptibility during the adolescent period, but with the current greater interest in the effects of hormonally active agents, more information is becoming available. 

Milgrom and co-workers [105] recently developed an immunogold method for detection of PR in the rabbit uterus and have examined the effect of hormone addition on receptor localization at the ultrastructural level. PR were found to be predominantly nuclear in the presence and absence of hormone, but a small amount was detectable in the cytoplasm which was not apparent at the light microscopical level. These cytoplasmic PR were localized over endoplasmic reticulum and clusters of free ribosomes and may likely represent newly synthesized protein. No PR were located in the plasma membrane. Within the nucleus, unoccupied PR were associated with condensed chromatin which became more dispersed after hormone addition. These ultrastructural studies indicate that steroid-free PR translocate from their site of synthesis in the cytoplasm to the nucleus in a hormone independent manner, and that addition of hormone changes their intranuclear localization. 

Receptors for protein hormones can be coupled to different transducing systems. Most of the data from studies approximately 10 years ago showed that many receptors are coupled to the adenylate cyclase system. However in the early 1980s it became clear that calcium fluxes and phospholipid turnover could also be important in conveying hormonal signals. During the last few years the number of papers describing the effects of hormones on phospholipid metabolism and calcium fluxes has increased tremendously and has outnumbered studies on cyclic AMP. 

Many other GPCRs mediate the effects of hormones and NTs involved in a wide variety of responses. Some of these are also targets for plant defensive compounds (Table 5.8) and are listed alphabetically for convenience in the outline presented below. Note that all of the hormones listed below are peptides except for (a) ATP, (c) anandamide, (j) melatonin and (p) some non-peptide sigma receptor ligands. 

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