Androgen

A detrimental effect caused by androgens is also reported. Blockade of the endogenous testosterone by flutamide or depletion of testosterone (castration) improved myocardial function of the perfused rat hearts subjected to ischemia and reperfusion. This response was associated with decreased caspase l, caspase-3, caspase-11, decreased TNF-alpha, IL-1 beta, IL-6, decreased ischemia and reperfusion induced p38 MAPK activation and increased Bcl-2 expression in castrated and flutamide treated males.15 Accordingly, supraphysiological doses of nandrolone taken during exercise or under sedentary conditions increased myocardial susceptibility to ischemia and reperfusion injury in perfused rat hearts. Pre-ischemic c-AMP concentrations and pre-ischemic and reperfusion TNF-alpha concentrations were found to be increased in those hearts.16 

Male and female hormones are produced primarily in the gonads. Androgens are synthesized in the testes in the male. In the female, the ovaries are the principal sites of estrogen and progestin production. As discussed in Chapter 29, small amounts of sex-related hormones are also produced in the adrenal cortex in both sexes, which accounts for the fact that small amounts of hormones of the opposite sex are seen in females and males that is, low testosterone levels are seen in females, and males produce small quantities of estrogen. However, under normal conditions, the amounts of sex-related hormones produced by the adrenal cortex are usually too small to produce significant physiologic effects. 

This chapter first discusses the physiologic role of the male hormones and the pharmacologic use of natural and synthetic androgens. The physiologic and pharmacologic characteristics of the female hormones are then addressed. As these discussions indicate, there are several aspects of male and female hormones that should concern physical therapists and occupational therapists. Rehabilitation patients may use these agents for approved purposes, for example, female hormones as contraceptives. These agents may also be 

1) a-Hydroxylation results in ER-binding and agonist activity (in contrast to the therapeutically desired antagonist activity). 

2) Addition of a hydrophobic group favors antagonist activity. 

3) Inclusion of bulky and N-containing substituents favors both antagonism and cytotoxicity. 

Testosterone, the male sex hormone, is responsible for the development and maintenance of the male sex organs (the penis, prostate gland, seminal vesicle, and vas deferens) and secondary sex characteristics. In addition, testosterone has anabolic effects. Similar to progesterone, testosterone is metabolized very rapidly by the liver by the first-pass mechanism, and hence requires structural 

Ethinyl estradiol and norgestrel (combination available as Ovral) Ethinyl estradiol Conjugated estrogens Estrone 

100 (lg ethinyl estradiol and 1 mg norgestrel (two Ovral tablets) taken twice 12 h apart 2.5 mg twice daily for 5 d 10 mg three times daily for 5 d 5 mg three times daily for 5 d 25 mg twice daily for 5 d 

Testosterone and its derivatives are used in the treatment of hypogonadism (eunuchoidism), hypopituitarism, accelerated growth, aging in men, osteoporosis, anemia, endometriosis, promotion of anabolism, suppression of lactation, and breast carcinoma. 

Hormonal therapy with testosterone should be reserved primarily for patients with hypogonadal disorders. There are two important warnings about the indiscriminate use of intramuscular testosterone in patients with serum testosterone levels in the normal range. First, many impotent patients are older and may have adenocarcinoma of the prostate, thus exogenous testosterone may accelerate the growth of the neoplasm. Second, although testosterone may induce a marked increase in libido, patients may still be unable to achieve adequate erection. 

Experiments with testieular extract has more or less enjoyed a ehequered eareer. Veronoff successfully transplanted tested from monkeys into elderly men and claimed to rejuvenate them. Likewise, ligature of vas deferens whieh is known to cause atrophy of spermatogenie tissue and indireetly hypertrophy ofintestinal tissue which secrete testosterone. Another researeher Steinaeh earned out similar studies by ligaturing the vas deferens and obtained identical results. 

Androgens besides showing a specifie aetion on gonads, also stimulate produetion of elements that are absolutely essential for all tissue growth. This eharacteristie whieh the androgens share with other steroidal hormones, such as corticosterones and oestrogens has paved the way towards synthesis of newer steroids that possess mainly metabolie aetivity without androgenie effeet. 

Androsterone (m.p. 185°C) is anatnrally occurring androgen that may be isolated from male urine. It can also be synthesized from epi-cholestanyl acetate as given below  

It may be synthesized from epi-eholestanyl acetate at two stages first, by its oxidation with chromium-6-oxide and secondly, by subjeeting the resulting product to hydrolysis to yield the desired product. 

Butanandt and co-workers (1931) first isolated androsterone (15 mg) from 15,000 litres of urine. B. Testosterone INN, BAN, USAN, 

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NaturaHy occurring and synthetic estrogens and androgens have been extensively and safely used to improve efficiency and carcass composition ia growing beef catde in the United States since the early 1950s. Several anaboHc steroid implants have been approved for use in beef catde in the United States, but only one, zeranol [55331-29-8] is approved for use in lambs. Anabolic steroids are not used for growth regulation in swine or poultry (see Steroids). 

Classification of the anabolic steroids is based on chemical stmctures and associated actions. A review of the biosynthesis and metabolism of the naturally occurring estrogens and androgens is available (1). Names, descriptions, approval dates, and recommended doses of the commercial products are found in References 1, 8, and 9. Although steroids may be orally active, the FDA approved mode of adrninistration is the subcutaneous implant. Effective dose is lower with implant rather than oral adrninistration. 

Extracts of corpora lutea were known ia the early tweatieth ceatury to inhibit ovulatioa ia animals. Pure progesterone (3), the active component of the extracts, was isolated ia 1934 and its stmcture reported (15). Several problems limited its use and drove efforts to develop progesterone analogues, ie, it was available only ia small quantities from animal sources, was not orally active, and was discovered to cause androgenic side effects. 

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

Hormonal effects on the aging process have been areas of current interest. The intricacies of the interaction of the various hormones are undoubtedly involved in the aging process and hence these hormones could be called antiaging agents. Both androgens and estrogens have been studied. Low level estrogen replacement therapy (ERT) has been used to treat postmenopausal women. 

Steroid hormones can be subdivided into sex hormones (androgens, estrogens, and progestins) and corticosteroids (glucocorticoids and mineralocorticoids). 

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