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Rat oral mucosa microsomal Δ 4-3-ketosteroid-5α-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/ or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates.

Oral administration of medroxyprogesterone acetate to 4 normal male and 3 normal female subjects was found to produce a significant increase in the metabolic clearance rate of testosterone in 6 of the 7 subjects. The plasma levels and production rates of testosterone decreased markedly in the males. The females tended to show a decrease in the plasma concentration of testosterone with no change in the production rate of the steroid. Although there was an over-all decrease in the percentage binding of testosterone for the group, individual responses were variable in degree and did not necessarily correlate with the alterations in the metabolic clearance rate of the steroid. Plasma LH levels fell during the administration of medroxyprogesterone acetate in 6 of the 7 subjects. Plasma FSH, however, decreased in only 1 subject (postmenopausal female). Medroxyprogesterone acetate increased rat hepatic testosterone A-ring reductase activity almost 4-fold. Moreover, the drug interfered with the growth-pr...

Within 3 hr after the intraperitoneal administration of hydrocortisone to female rats, a new leucine-accepting tRNA and a new leucyl-tRNA synthetase activity appear in the liver cytosol. The new isoaccepting tRNA can be acylated only with the synthetase derived from livers of hormone-treated animals. Both components are transient; by 12 hr after hydrocortisone administration, the isoaccepting tRNA and its synthetase disappear from livers of treated animals.

Male alcoholics often suffer from features of hypogonadism related to abnormal metabolism of sex steroids. Since the activity of testosterone reductases is rate limiting for testosterone metabolism in the liver, the effect of prolonged ethanol consumption by rats and human volunteers on the activities of these microsomal and cytosolic enzymes was studied. In rats, long-term ethanol ingestion doubled microsomal 5alpha-testosterone reductase activity, a major pathway for testosterone metabolism, while in human volunteers the activity was increased two- to fivefold. These changes may play a role in the altered androgenic activity of the chronic alcoholic.

Administration of medroxyprogesterone acetate (MPA) to castrated male rats inhibited the testosterone mediated growth of prostate and seminal vesicle. MPA, however, failed to increase the activity of testosterone A-ring reductase in the prostate in contrast to its marked inductive effect on the liver enzyme. MPA treatment caused a diminished uptake of radioactivity by the prostate and seminal vesicle in vivo after a single injection of 3H-testosterone, as well as, a lower plasma level of the labeled hormone. However, in vitro incubation of prostatic tissue derived from MPA treated rats with 3H-testosterone showed no local interference with the uptake of radioactivity. It appears, that the anti-androgenic effect of MPA can be explained on the basis of induction of hepatic testosterone reductase activity which in turn increases the catabolism of the hormone, leading to its lower plasma concentration and consequently to a lower target tissue uptake of testosterone. (Endocrinology 93: 417, 1973)

Administration of medroxyprogesterone acetate (MPA) to male rats causes a significant (2-3-fold) increase in the activity of hepatic testosterone A-ring reductase. This was demonstrated by employing assays that measured an increase in disappearance of testosterone and/ or an increase in its reduced metabolites. Progesterone and its derivatives were also capable of increasing the reductase activity. Fasting or fed state, castration or adrenalectomy did not interfere with the effect of MPA, nor did the administration of phenobarbital or cortisol cause a rise in the reductase level. MPA also significantly increased the rate of reduction of Δ4-androstenedione, cortisol, progesterone and MPA itself (all Δ4-3-ketosteroids) when used as substrates in vitro. Cytoplasmic fractionation revealed that the MPA stimulated increase in reductase activity is restricted to the microsomes, indicating that only the Sa-oxidoreductase activity is affected. Simultaneous administration of actinomycin-D with MPA resulted in a com...

6α-Hydroxycortisol was found to have a cortisol-like activity in inducing rat hepatic tryptophan oxygenase. 6β-Hydroxycortisol was without this effect. Neither 6β-hydroxycortisol nor o,p'-DDD had any cortisol inhibitory activity in this enzyme system. (Endocrinology 83: 384, 1968)