Concentrations of steroid hormones

Various analytical methods of extremely high sensitivity are now available to measure minute concentrations of steroid hormones in blood. GC is frequently preferred over other measurement principles because of its high sensitivity and reliability. Since some of these GC procedures are technically involved, they are used more often in biomedical research laboratories than in a routine clinical environment. 

Changes in the concentrations of steroid hormones in plasma have implications for a range of chronic diseases, snch as osteoporosis, arthritis, and cardiovascular disease. Studies investigating these diseases have been carried ont mainly in animal models, and have been reviewed elsewhere (Nielsen, 1991, 1997, 2000, 2008 Mastromatteo and Sullivan, 1994 Naghii and Samman, 1993 Samman et al., 1998 Devirian and Volpe, 2003). 

As discussed in the previous section, steroid and thyroid hormones are transported in the blood bound to plasma proteins. The serum concentrations of free hormone (H), plasma protein (P), and bound hormone (HP) are in equilibrium ... 

Brain delivery of steroid hormones is also of interest to medicinal chemists. Again, most data available on CDSs of steroids pertain to rates of oxidation of the dihydropyridine carrier, to blood and brain concentrations, and to pharmacological activities. The latter can then be taken as proof of efficient cerebral hydrolysis of the pyridinium metabolite. Thus, the dihydrotrigonelline carrier allowed good brain delivery of estradiol and some other estrogens [181][182],... 

A deficiency of liver function reduces metabolism of steroid hormones so that the blood concentration of oestrogens in men is increased. 

In addition to these major processes, many other chemical events also occur. Mitochondria concentrate Ca2+ ions and control the entrance and exit of Na+, K+, dicarboxylates, amino acids, ADP, P and ATP, and many other substances.16 Thus, they exert regulatory functions both on catabolic and biosynthetic sequences. The glycine decarboxylase system (Fig. 15-20) is found in the mitochondrial matrix and is especially active in plant mitochondria (Fig. 23-37). Several cytochrome P450-dependent hydroxylation reactions, important to the biosynthesis and catabolism of steroid hormones and... 

The occupancy of hormone receptors can fluctuate greatly and is ultimately determined by the concentration of free hormone in the blood. The major determinants of hormone concentrations are (1) the rate of hormone secretion from endocrine cells and (2) the rate of hormone removal by clearance or metabolic inactivation. As we have seen, most hormones (with the exception of steroids) are stored in secretory granules. When the hormone is needed, the granule membranes fuse with the plasma membrane to liberate their contents into the bloodstream. This event is triggered by signals from other hormones or by neural signals. Stimulation of hormonal secretion is usually coupled with an increase of hormone synthesis, so that hormonal stores are replenished. 

Thyroid hormones and most steroid hormones are associated with carrier proteins in the serum. The carrier proteins are called, appropriately, thyroxine-binding globulin, transcortin (for cortisol), and sex-steroid-binding protein. These proteins have a high affinity (Kd 10—9— 10 8 m) for their respective hormones. They buffer the concentration of free hormone and retard hormone degradation and excretion. The carrier proteins are distinguishable from the intracellular receptors for these hormones. 

Many studies have shown that lactation is not adversely affected by depot medroxyprogesterone acetate and that breast-milk production may even be increased (35). Because of the low binding affinity of medroxyprogesterone to sex hormone binding globulin, the concentration of steroids in the milk is close to that in the maternal plasma, unlike the 19-nortestosterone derivatives. 

Fire Master FF-1 caused a longer sexual cycle in monkeys [5], and PBBs caused decreased egg production and nesting behaviour in Japanese quail [86]. One recent study reported that in mice PBB (di-BBs and tetra-BBs) reduced the in vitro fertilisation rate at higher dosages. Furthermore, an increased incidence of abnormal two-cell embryos and degenerative ococytes was observed at the 1 and 10 mg/ml concentration of PBB [87]. PBBs also affect the regulation of steroid hormones. The extent depends on the species as well as the dose and duration of exposure. 

A second group of steroid hormones includes the adrenal cortical steroids. Three examples of these hormones are cortisone, cortisol, and aldosterone. All of these compounds are synthesized in the outer layer of the adrenal gland. Cortisone and cortisol serve as anti-inflammatory agents and they also regulate carbohydrate metabolism. Aldosterone regulates blood pressure and volume by controlling the concentration of Na and in body fluids. 

The nongenomic and nonreceptor responses to steroids will not be covered here. Instead, we will concentrate on the mechanisms by which the classic steroid hormones alter gene transcription via their intracellular cognate receptor protein. We will discuss only the primary effects of steroid hormones, which are those rapid (15-30 min) events that lead to changes in gene transcription without any requirement for protein synthesis. It should be remembered that at a sufficiently precise level, the mechanism of action of each class of steroid hormone is different from that of the others. 

Luteinizing hormone-releasing hormone (LHRH) is used in the treatment of infertility (1). It induces pulsatile release of gonadotropin, and excessive stimulation can result. However, if used over a period of time, the receptors cease to respond and there can be a fall in the concentrations of luteinizing hormone and follicle-stimulating hormone and a fall in sex steroid concentrations to the castrato range. 

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