Dynamics of Steroid Secretions in Rats

Abstract

In spite of the vast information available on hormone secretions and their levels in blood, there is a paucity of information in age related changes in the dynamics of steroid metabolism in male rats. Also, few investigations exist concerning the metabolic clearance rates (M.C.R.) of steroids in blood of female rats. This thesis consists of two parts, the first part deals with changes in M.C.R. in aging male rats and the second part in pregnant rats. It examined these changes relative to testosterone (T), estradiol (E_2), and progesterone (P), using the non-equilibrium single dose injection method. 3H-steroids were administered via the cannulated jugular vein. Sequential blood samplings were obtained up to 150 min. 3H-steroids were extracted, processed by Sephadex LH-20 column chromatography and the radioactive steroids were quantified with liquid scintillation spectrometer. Results were analysed by the computer using the 'peel-off' method for a two-compartment model. In aging studies M.C.R. and production rate of T were found significantly higher in young male rats when compared with aged rats. Half-life (t ½ ?) in the outer pool was significantly higher in the old rats than in young rats while t ½ ? in the inner pool did not change significantly between both aging groups. However, the M.C.R. for E_2 and P remained unchanged in both groups. Chronically castrated animals of both age groups showed significant decline in M.C.R. of T and increased in t ½ ? when compared with their respective intact controls. M.C.R. of T in young or old castrated rats previously injected with T were restored to values similar to those young intact rats. From these results it is concluded that the age-related changes in M.C.R. of testosterone are due to an interaction of testicular dysfunction and androgen status of animal. In the second part of the study, non-pregnant, pregnant (D-10 and D-20) and post-partum rats were used. The M.C.R. of E2 in D-20 rats was found to be significantly higher when compared with other groups. In post-partum rats the M.C.R. of E2 was significantly higher than those of non-pregnancy or D-10 of pregnancy. All values for t ½ ? of E_2 were found to be similar for all groups. t ½ ? of E_2 in D-20 was greatly lower than both non-pregnancy and D-10 gestation. However, the M.C.R. of P remained unchanged in all female groups. The fast component (t ½ ?) of P was significantly higher in post-partum than in D-10, meanwhile it did not change in other groups. The slow component (t ½ ?) of P was higher in non-pregnant rats compared with D-10, other groups remained unchanged. The M.C.R. of T was significantly lower in non-pregnant rats than in post-partum rats, other groups remain unchanged. t ½ ? of T was significantly higher in post-partum rats than in D-20 and D-10 of pregnancy. There was no change in t ½ ? of T between all groups. It is evident that changes in metabolic clearance rates of different steroids vary according to their respective roles in pregnancy reflecting physiological demands.