Effects of Steroids in Human Body

The sterol, cholesterol, serves as the major sex hormone precursor. This compound--which is derived from acetyl coenzyme A--represents an integral component of eukaryotic membranes (14:474-482). It gives rise to fin different types of steroid hormones. These include the following categories: (1) the progestagens; (2) the glucocorticoids; (3) the mineralocorticoids; (4) the androgens; and (5) the estrogens. These hormones atomic number 18 entirely somewhat similar in social organisation: For example, all reserve the "four-ring structure of the sterol nucleus (15:656-657). Despite this structural similarity, however, the respective(a) steroid hormones have distinctly different functions.

The first gradation in the synthesis of steroid hormones is stimulated by stimulative hormone secretion in the anterior pituitary. The chemical structure of cholesterol contains 27 carbon atoms. In contrast, the steroid hormones are comprised of less than 21 carbon atoms. Hence, the synthesis of steroids initially requires the removal of a C6 side chain. First, cholesterol's C-20 and C-22 atoms are hydroxylated to give 20(,22-dihydroxycholesterol. Then, the bond amid C-20 and C-22 is cleaved by desmolase. The three re sufficeions ultimately form the "key talk terms in the synthesis of steroid hormones," pregnenolone (14:474-482).

The transformation of pregnenolone to progesterone involves cardinal d

Steroid hydroxylation can to boot be inhibited by various compounds. For instance, Purba et al. (1987) found that some(prenominal) drugs and steroids act as competitive inhibitors of ethinyl estradiol 2-hydroxylation. Moreover, such substances as primaquine and tolbutamide act as noncompetitive inhibitors of the reaction. In addition, mechanism-based or "suicide" inactivation of cytochrome P450 can be accomplished by the acetylenic steroids (6:2159-2162). In fact, the acetylenic analogs of androstenedione (Plomestane) and deoxycorticosterone (18-acetylenic deoxycorticosterone) represent the first "rationally, designed, enzyme-activated inhibitors of aromatase (11:17-34)." The compounds act as pseudo-substrates for the targeted enzymes.

Then, it has been hypothesized that when the monooxygenase de colorfuls an activated oxygen to the acetylenic bond, it forms a flitting re spry oxirene. This intermediate is past able to covalently bind to the enzyme mote (11:17-34).

One steroid-like substance that undergoes hydroxylation reactions is vitamin D. Initially, cholesterol is converted to 7-dehydrocholesterol (pro-vitamin D3). This compound is then photolyzed by ultraviolet light to pre-vitamin D3. Eventually, pre-vitamin D3 spontaneously isomerizes to give vitamin D3. This compound, however, does not have any biologic activity. Rather, it must first be converted to an active form by hydroxylation reactions in the liver and kidneys. In the liver, hydroxylation of vitamin D3 gives 25-hydroxycholecalciferol. This compound is then transported to the kidneys and further hydroxylated to yield the active hormone, 1(,25-dihydroxycholecalciferol (15:1145-1146). This hormone acts in a synergistic manner with parathyroid gland hormone to increase serum Ca2+ (15:1145-1146).

3. Ball, P.; Knuppen, R. Formation, metabolism, and physiologic importance of catecholestrogens. American Journal of Obstetrics and Gynecology. 163 (6 Part 2):2163-2170; 1990, December.

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