Androstenedione, from dehydroepiandrosterone

In the placental tissue, there is an extensive formation of androstenedione from dehydroepiandrosterone, which is obtained mostly by the hydrolysis of dehydroepiandrosterone sulfate, which is biosynthesized principally in the fetal compartment. On the other hand, as was indicated before (Section 111, B, 1, a), in the placental compartment very few if any Cw steroids arc formed from Cm steroids by side-chain cleavage (Warren and Cheatum, 1964 Jaffe et al., 1965). Also, since androstenedione is not a good substrate for 17d-rcductasc, it can be assumed that most of the placental t( Stosterone originates from fetal androstenediol (Uell Acqua et al., 1966, 1967a,b). It is interesting to note that thi.s latter steroid is a normal const.ituent of cord blood (Kberlein, 1965). 

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. 

Furthermore Tait and co-workers [322] pointed out the marked difference in the urinary and blood production rates of testosterone obtained in women after injection of radioactive testosterone. He concluded that steroids produced from dehydroepiandrosterone contribute little to the blood production rate of androstenedione and testosterone in normal subjects [403]. According to Tait [324], all the blood production rate of androstenedione in the female and testosterone in the male is due to the same secreted steroid, while the blood production rate of testosterone in the female and androstenedione in the male is due about one-half to the same secreted steroid and one-half to converted precursor. The normal male secretes a ratio of testosterone to androstenedione of about 10 1 and the normal female secretes a ratio of androstenedione to testosterone of about 25 1. 

Testosterone and oestradiol are known as the sex steroid hormones. Testosterone is the principal androgen and is synthesized by the testes in the male. Oestradiol. which is secreted by the ovaries, varies w idely in concentration in plasma throughout the female menstrual cycle. Steroids with oestradiol-like action arecalledoestrogens. Progesterone is a product ofthe ovary and is secreted when a corpus lutcum forms after ovulation. Normal female plasma also contains testosterone, about half of which comes from the ovary and half from peripheral conversion of androstenedione and dehydroepiandrosterone (DHA) sulphate which are secreted by the adrenal cortex. Some oestradiol is present in low concentration in normal male plasma. 

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.)...

Overall, other adrenal androgens also show a progressive decrease in urinary excretion in both men and women. Thus, the mean 17-ketosteroid urine levels of elderly people are about 50% of those in young adults. This is primarily secondary to decreased dehydroepiandrosterone (DHEA) and androsterone production. In men, about one-third of the daily 17-ketosteroids are of testicular origen, the remainder being mainly from the adrenals. Androstenedione is a prehormone for testosterone. 

It has been shown that hormones are not exclusive products of the glands but are also formed in metabolizing organs. These hormones, however, contrary to the classical hormones, are not secreted into the blood. It has been established that testosterone formed in the liver from androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate does not enter the blood [305,323,388]. It has also been established that secreted and metabolically produced testosterone do not have the same metabolism [169, 311]. 

In most mammals, estrogens (female sex steroid hormones) are synthesized from cholesterol using the parent ring structure, cyclopentanoperhydrophenan-threne of the estrane series. The steroidogenic pathway includes the production of the androgenic precursors dehydroepiandrosterone and androstenedione, the latter of which is converted to testosterone, then to estradiol-17/i. This requires aromatization of these andogenic precursors by an aromatase enzyme complex. The major source of estrogen in postmenopausal women is the conversion of androstenedione to estrone by aromatase activity... 

---