Estradiol , consider hormonal

The most significant metabolic product of testosterone is DHT, since in many tissues, including prostate, external genitalia, and some areas of the skin, this is the active form of the hormone. The plasma content of DHT in the adult male is about one-tenth that of testosterone, and approximately 400 ig of DHT is produced daily as compared with about 5 mg of testosterone. About 50-100 ig of DHT are secreted by the testes. The rest is produced peripherally from testosterone in a reaction catalyzed by the NADPH-depen-dent 5oi-reductase (Figure 42-6). Testosterone can thus be considered a prohormone, since it is converted into a much more potent compound (dihydrotestosterone) and since most of this conversion occurs outside the testes. Some estradiol is formed from the peripheral aromatization of testosterone, particularly in males. 

Steroid hormones form a group of pollutants that includes natural hormones such as estradiol, testosterone, and their metabolites as well as several synthetic analogues. Steroid hormones used as growth promoters have already been found in water and sediments (Lai et al. 2000 Thorpe et al. 2003), and their adsorption properties on earth materials have been considered. Lee et al. (2003) report batch experiments where simultaneous sorption of three hormones (17- 3-estradiol, 17-a-ethyl estradiol, and testosterone) on four midwestem U.S. soils and a freshwater sediment were performed. Apparent sorption equilibria were reached within a few hours. Sorption isotherms generally were linear for the chemicals studied on one of these soils (Drummer soil), ranged from 23.4 to 83.2 L kg and log ranged... 

In rats ammonium perfluorooctanoate induced hepatomegaly that was more pronounced in the male than in the female. Male rats are thought to be more sensitive to the toxic effects of ammonium perfluorooctanoate because of their slower excretion rate. The rapid excretion by female rats is due to active renal tubular secretion, which is considered to be hormonally controlled by estradiol and testosterone levels. The hepatomegaly was hypertrophic rather than hyperplastic and involved proliferation of peroxisomes. 

We next look at an example that illustrates how transcription factors can stimulate changes in chromatin structure that affect transcription. We will consider in some detail the system that detects and responds to estrogens. Synthesized and released by the ovaries, estrogens, such as estradiol, are cholesterol derived, steroid hormones (p. 753). They are required for the development of female secondary sex characteristics and, along with progesterone, participate in the ovarian cycle. 

Anastrozole (Fig. 46.11) is a potent and highly selective, nonsteroidal aromatase inhibitor utilized in the treatment of advanced breast cancer that is hormone-responsive. It is considered to be second-line therapy (after tamoxifen) in the treatment of postmenopausal breast cancer. Anastrozole. a benzyltriazole derivative, competes with the natural substrate for binding to the active site of the aromatase. The mechanism of enzyme inhibition resides in the coordination of the triazole ring with the heme iron atom of the aromatase enzyme complex (161,162). This coordination ultimately prevents aromatization of androgens into estrogens and, therefore, deprives the tumor of estrogen. This effect is reversible. In the presence of anastrozole. estradiol levels are reduced to undetectable levels, with no adverse effects on levels of any other hormone, including cortisol and aldosterone. 

The process of deposition of calcium in bone is not fully understood, but alkaline phosphatase, vitamin D, vitamin C, and probably other factors are of great importance. Removal of mineral from bone and maintenance of normal serum calcium concentration is dependent largely on the activity of the parathyroid hormone. Albright considers that the primary effect of the parathyroid hormone is an increase in phosphorus excretion (Chapter 21). This is followed by a decrease in serum phosphorus and resorption of phosphorus and calcium from bone. Other hormones also influence utilization of calcium and phosphorus (Chapter 21). In hyperthyroidism, excretion of calcium and phosphorus is increased and osteoporosis may develop. The steroid hormones, e.g., estradiol and testosterone, decrease calcium and phosphorus excretion and may therefore be useful in the therapy of postmenopausal and senile osteoporosis. 

The first clear-cut effect of an estri enic hormone added in vitro to an enzyme system was reported by Hagerman and Villee (1953) and Villee and Hagerman (1953), who showed that the addition of estradiol-17/3 to slices of human endometrium or placenta incubated in vitro produced an increased rate of oxidative metabolism. In placental homogenates the locus of action of estradiol was considered to be a diphosphopyridine nucleotide-linked isocitric dehydrogenase present in the soluble fraction (Villee and Gordon, 1955). Triphosphopyridine nucleotide did not replace diphosphopyridine nucleotide (Villee, 1955), and a divalent metal cation is required for full... 

Important estrogens are estrone, 17fi-estradiol, and 3,16a,17ff-estriol. Estrone easily converts to estradiol, which is considered to be the true female sex hormone. Eor physiological properties see Chapt. XX. 

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