Androgens, Plasma

Singh SK, Pandey RS. 1990. Effect of sub-chronic endosulfan exposures on plasma gonadotrophins, testosterone, testicular testosterone and enzymes of androgen biosynthesis in rat. Indian J Exp Biol 28 953-956. 

Prophylactic treatment of Cl INH deficiency consists of Cl INH replacement infusions, androgens (danazol, stanozolol, oxymethalone) or antifibrinolytic agents. Acute treatment employs Cl INH replacement (where available), fresh-frozen plasma, and placement of an airway when significant airway obstruction is evident. Abdominal attacks require IV fluid, analgesics, and watchful waiting . 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

Androgenic deficiency in male rats given a single oral dose of 15 pg 2,3,7,8-TCDD/kg BW was evident as early as 2 days posttreatment, with persistence up to 12 days. These deficiencies may account for male reproductive pathology and dysfunction in rats treated with overtly toxic doses of TCDD. Findings included depression in plasma testosterone concentrations, as well as decreased weight of seminal vesicles (by 68%), ventral prostate gland (by 48%), testes, and epididymis (Moore et al. 1985). 

Metyrapone inhibits 11-hydroxylase activity, resulting in inhibition of cortisol synthesis. Initially, patients can demonstrate an increase in plasma ACTH concentrations because of a sudden drop in cortisol. This can cause an increase in androgenic and mineralocorticoid hormones resulting in hypertension, acne, and hirsutism. Nausea, vomiting, vertigo, headache, dizziness, abdominal discomfort, and allergic rash have been reported after oral administration. 

Endogenous and exogenous androgens can be derivatized with trimethylsilyl (TMS) for hydroxy functions and by 0-methylation for ketones, and analyzed with GC-FID or GC-MS (Shimada et al., 2001). MS is more prevalent due to unequivocal identification and greatly increased sensitivity but FID is still used in laboratories for some steroids. Sterols have typically been analyzed by GC-FID and GC-MS with derivatization to optimize peak shape (Shimada et al., 2001), and bile acids can be derivatized with M-butyl ester-TMS ether and analyzed by GC-FID from plasma samples (Batta et al., 1998). Juricskay and Telegdy (2000) reported an assay capable of analyzing 28 steroids in urine samples using GC-FID. 

HRT (hormone replacement therapy) administration of estrogens to women or androgens to men who, due to menopause or age, have decreased levels of these plasma steroids. 

Determination of Estrogens, Androgens, Progesterone, and Related Steroids in Human Plasma and Urine Ian E. Bush... 

Concentrations of plasma testosterone and other androgens vary throughout the day in both sexes whether such variation is simply random or fits a repeatable diurnal pattern is a matter of debate. Compared with the diurnal variation seen with cortisol, plasma testosterone concentrations are reasonably constant. Plasma androgen concentrations also vary greatly in women through the menstrual cycle, with peak levels seen in the luteal phase. 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble compounds that are excreted by the kidney as the urinary 17-ketosteroids. 

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

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