Dehydroepiandrosterone, from pregnenolone

Hydrolysis of the acetate (71) followed by Oppenauer oxidation gives B-norcholest-4-en-3-one in high yield. An analogous reaction sequence can be used to prepare B-norprogesterone and derivatives of B-nortestosterone from pregnenolone acetate and dehydroepiandrosterone acetate, respectively."" ... 

The steroid Ci7(20)lyase is an enzyme that is involved in the biosynthesis of andro-stenedione and of dehydroepiandrosterone from progesterone and pregnenolone, respectively. As androgen and estrogen hormones are necessary for the growth of tumors, this enzyme is a potential therapeutic target for the treatment of prostate cancer and in hormone-dependent breast cancers. 

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

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. 

Fig. 29.13 GC-MS chromatogram of neutral steroids in meat. Androgens (fortified, 0.2-0.5 ppb) 1, a-androsterone 2, dehydroepiandrosterone 3, epitestosterone 4, dihydrotestosterone 5, androstenedione 6, testosterone IS, methyltestosterone. Progestagens (fortified) 7,7a, pregnenolone (2.1 ppb) 8, progesterone (0.4 ppb) 9, hydroxyprogesterone (0.3 ppb). (Reprinted from Ref. 452, with permission from Elsevier Science.)...

The development of the various adrenal enzymes in the fetal adrenal may also be of considerable significance in interpreting the lack of activity observed after birth. jS-Hydroxysteroid dehydrogenase is low in fetal liver thus, the pathway prevails (pregnenolone— dehydroepiandrosterone), and cortisol synthesis is low. The relatively large adrenals found in utero may result from compensatory hyperplasia in response to low cortisol secretion. In early embryonic life, 21- and 11-hydroxylase activities are low, but they increase with the age of the fetus. 

Dehydroepiandrosterone (DHEA) levels are detennined in dietary supplentents using a Cig column (A = 292 nm) and a 60/40 acetonitrile/water (25 mM KH2PO4 to pH 3.5 with H3PO4) mobile phase [1119]. DHEA was resolved from testosterone, androsterone, and pregnenolone and eluted in <10min. Calibration standards were run from 2 to 50pg/mL. Detection and quantitation limits were reported as 0.9(ig/mL and 3.3pg/mL, respectively. 

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