Rate Of Corticosterone Production Research Articles

Δ4-5α-HYDROGENASE DER LEBER UND NEBENNIERENRINDEN-AKTIVITÄT UNTER EINFLUSS VON SCHILDDRÜSENHORMON

ABSTRACT In experiments with male rats the in vivo effects of thyroxine (T4) and triiodothyronine (T3) on the following parameters were investigated: the microsomal Δ4-5α-hydrogenase activity of the liver, the adrenal weight and the in vitro corticosterone production rate. Either thyroid hormone leads to the known increase in the cortisone reduction rate. However, there are two different mechanisms underlying this effect. While the effect of T4 after two or three days of treatment is due to an increase in the production of reduced NADP by the liver cell with no change in the Δ4-5α-hydrogenase activity (McGuire & Tomkins 1959), treatment for only two days with T3 causes an increase in microsomal activity. The activity of the microsomal preparation without additions is zero for both the control and the T3 treated animals. If increasing quantities of NADP are added together with glucose-6-phosphate and glucose-6-phosphate dehydrogenase, then for each addition of NADP up to the maximum value the activity of the Δ4-5α-hydrogenase of the treated animals is always considerably higher by the same percentage than that of the controls. With animals possessing low Δ4-5α-hydrogenase activity treatment with T3 leads to a greater percentage increase in the enzyme activity than with animals having higher hydrogenase activities. There exists a very close correlation (r = 0.94) between hydrogenase activity and its percentage increase due to T3 administration. The regression-line indicates that with hydrogenase activities greater than 12 T3 is without effect. This leads to the view that the hepatic action of T3 is to promote steroid hydrogenation up to a fixed turnover rate. Although the increase in the adrenal weight was the same with either thyroid hormone, only T3, not T4, was simultaneously effective in raising corticosterone production rate in vitro. Thus, an increase in the adrenal weight is not in any case the expression of an enhanced hormone secretion rate. The fact that the administration of T4 significantly increases Δ4-5α-hydrogenase activity and adrenal weight without concomitant increase in corticosterone production rate must be regarded as evidence against the assumption that the adrenal effect of T4 is simply the consequence of the primary acceleration of corticosteroid turnover in the liver.

Investigations on the mechanisms of reduced aldosterone production caused by the administration of hydrocortisone

In vitro aldosterone production in rat adrenal slices treated with 2×5 mg of hydrocortisone daily, for five and ten days, respectively, was found to be reduced. The rate of corticosterone production also diminished, but, to a lesser degree. Progesterone and corticosterone added to the incubation medium augmented the rate of aldosterone and cortico-sterone production to the same extent as in the controls. These findings suggest that administration of the exogenous cotricosteroid has an inhibitory effect upon progesterone synthesis since the conversion progesterone → corticosterone → aldosterone is not interferred with.

CORTICOSTEROID-UMSATZ UND CORTICOSTEROID-PRODUKTION BEI RATTEN UNTER DER BEHANDLUNG MIT ANABOLEN STEROIDEN

ABSTRACT After the administration of anabolic steroids to adult female rats in daily doses of 1 mg per animal for 14 days, the following parameters were investigated: the rate of the Δ4-5α-hydrogenase-catalyzed cortisone reduction in liver slices and microsomal fractions, the adrenal weight and the in vitro corticosterone production rate. Among the steroids tested, only 17α-methyl-testosterone and 17α-ethyl-19-nor-testosterone were effective in lowering significantly cortisone reduction rate by liver slices with concomitant decreases in microsomal Δ4-5α-hydrogenase-activity. Testosterone, 19-nor-testosterone, 17α-ethinyl-19-nor-testosterone, 17α-methyl-17β-hydroxy-androsta-1,4-dien-3-one and 1-methyl-17β-hydroxy-androst-1-en-3-one were ineffective or only slightly effective. Adrenal weight and absolute corticosterone production rate (μg/60 min per animal) were decreased after treatment with 17α-methyl-testosterone, 17α-ethyl-19-nor-testosterone and 1-methyl-17β-hydroxy-androst-1-en-3-one. Corticosterone production was decreased with 17α-ethinyl-19-nor-testosterone in spite of an unchanged adrenal weight. The relative corticosterone production rate (μg/60 min · 100 mg adrenal) was in any cases unaffected. According to these results there exists – with the exception of 17α-ethinyl-19-nor-testosterone – a strict parallelism between corticosteroid turnover and corticosterone production rate: unchanged turnover is correlated with unchanged corticosterone production rate, while a decreased turnover is correlated with decreased adrenal activity. The protein-anabolic effect of certain anabolic steroids may be partly due to an anti-catabolic action of these compounds resulting from a decreased corticosteroid inactivation and production rate. Possible mechanisms by which anabolic steroids may affect corticosteroid-balance are discussed.