Mechanism of action and conversions

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The testis has a dual function: spermatogenesis and the production of T. The latter takes places in the Leydig cells. The daily production of T in adulthood is about 5-7 mg. T diffuses passively into cells of the target organs of androgens. To exert its biologic action, it must bind to the androgen receptor, though there are also a number of biologic actions of T that do not require receptor activation. For some of its biologic actions T is a prohormone. After diffusion into the cell, T may be converted to 5 a-dihydrotestosterone (DHT) or estradiol. There are two types of 5 a-reductase enzymes that convert T to DHT. 5a reduc-tase type 1 is predominantly located in skin, liver, and brain whereas 5a reductase type 2 is almost exclusively distributed in the classical androgen-dependent organs such as prostate,seminal vesicles, and testicles. DHT and T bind to the same androgen receptor, although DHT has an approximately tenfold greater affinity for the receptor and its dissociation is slower, resulting in a considerably higher biopotency than T. The conversion of T to DHT can be viewed as an androgen amplification mechanism in organs that require a strong androgen action, such as the prostate. About 80% of DHT is produced in peripheral tissues and the remaining 20% is secreted directly by the testis. Furthermore, approximately 30-40 |g of estradiol is produced by the adult male, mainly in peripheral tissues, such as adipose tissue, bone, prostate, and brain. Insight into the biologic actions of estradiol in the male is rather recent. Estrogens have an important effect on the final phases of skeletal maturation and bone mineralization in puberty. In addition, from some studies in elderly men it appears that estrogen levels show a higher correlation with bone mineral density (BMD) than androgen levels [3]. Impaired estrogen action in men leads to dyslipidemia and to endothelial dysfunction. Observation in men with aromatase deficiency is linked to a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, steatosis hepatis, and signs of precocious atherogenesis, remedied by estrogen administration. Estrogen effects on the brain are also increasingly recognized [4]. Though the effects of estrogens in the male are undeniably biologically significant, estrogen deficiency as a clinical entity is sporadic in men. Since T is a precursor molecule for estradiol, it is usually associated with (severe) androgen deficiency.

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Supplements For Diabetics

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