Testosterone formation

Testosterone formation by reduction 17-keto into 17-beta-hydroxy group Baker s yeast... 

It is an excellent reagent for the formylation of alcohols. Thus testosterone and tosyl chloride in DMF give testosterone formate in 79% yield. The reagent reacts with arylamines to produce sulfonanilides (2) and/or formamidines (3). 

Aoyama, T., K. Korzekwa, K. Nagata, J. Gillette, H.V Gelboin, and F.J. Gonzalez (1989). cDNA-directed expression of rat testosterone 7c<-hydrox-ylase using the modified vaccinia virus, T7-RNA-polymerase system and evidence for 6D-hydroxylation and A -testosterone formation. Eur. J. Biochem. 181, 331-336. 

Murono, E. P., R. C. Derk, and Y. Akgul. 2006. In vivo exposure of young adult male rats to methoxychlor reduces serum testosterone levels and ex vivo leydig cell testosterone formation and cholesterol side-chain cleavage activity. Reprod. Toxicol. 21(2) 148-53. 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

Antiandrogens inhibit the formation of the DHT-receptor complex and thereby interfere with androgen-mediated action at the cellular level.22 Megestrol acetate, a progestational agent, also is available and has antiandrogen actions.21 Finally, the conversion of testosterone to DHT may be inhibited by 5-a-reductase inhibitors.6... 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

Korzekwa KR, Trager WF, Nagata K, et al. Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed formation of delta 6-testosterone from testosterone. Drug Metab Dispos 1990 18(6) 974-979. 

Bloch, E., Lew, M. and Klein, M. (1971). Studies on the inhibition of fetal androgen formation. Inhibition of testosterone synthesis in rat and rabbit fetal testes with observations on reproductive tract development. Endocrinology 89 16-31. 

Figure 19.8 A brief summary of the pathways for formation and secretion of oestradiol and progesterone within the cells of the follicle. Cholesterol is taken up by thecal cells in a complex with low density lipoprotein. In the thecal cells, cholesterol is converted to testosterone which is released to be taken up by granulosa cells where it is converted into oestradiol. For synthesis of progesterone in the granulosa cells, cholesterol is synthesised de novo within the cells from acetyl-CoA. In the follicle the enzyme aromatase, which produces the aromab c ring in the female sex hormones, is restricted to the granulosa cells. The reacrions that are stimulated by LH and FSH increase synthesis and, therefore, secretion of testosterone and increased synthesis of oestrogens and progesterone.

An exactly analogous enzymic transformation is encountered during the formation of oestrogen and androgen sex hormones, e.g. estradiol and testosterone respectively, where dehydroepiandrosterone is oxidized to androstenedione. 

The synthesis and degradation of muscle proteins are regulated by hormones. Cortisol leads to muscle degradation, while testosterone stimulates protein formation. Synthetic anabolics with a testosterone-like effect have repeatedly been used for doping purposes or for intensive muscle-building. 

Congenital defects in the biosynthesis of steroid hormones can lead to severe developmental disturbances, in the adrenogenital syndrome (AGS), which is relatively common, there is usually a defect in 21-hydroxylase, which is needed for synthesis of cortisol and aldosterone from progesterone. Reduced synthesis of this hormone leads to increased formation of testosterone, resulting in masculin-ization of female fetuses. With early diagnosis, this condition can be avoided by providing the mother with hormone treatment before birth. 

A highly modified methyl testosterone derivative also exhibits antiandrogenic activity. One synthesis of this compound involves initial alkylation of methyl testosterone (35) by means of strong base and methyl iodide to afford the 4,4-dimethyl derivative 6. Formylation with alkoxide and methyl formate leads to the 2-hydroxymethyl derivative 37. Reaction of this last with hydroxyl amine leads to formation of an isoxazole ring. There is then obtained azastene (38) . 

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