Gastrointestinal absorption of estrone sulfate in germfree and conventional rats

Abstract

Steroids are extensively excreted in the bile of rats. There was no significant difference in biliary excretion of steroid following administration of [ 3H]-estrone sulfate into the proximal small intestine (PSI) of conventional (CVL; 17.8 ± 6.2%; mean ± SD) or germfree (GF; 28.2 ± 5.3) rats. A similar finding resulted from administration into the distal small intestine (DSI)-CVL, 22.3 ± 11.8%; GF, 11.4 ± 3.7%. However, when the drug was given into the caecum, excretion in the bile of CVL rats after 5 h was 59.1% whereas in GF rats it was only 1.7%. When estrone was injected into the PSI and DSI of CVL and GF rats, absorption (as judged by excretion in bile) was more rapid than that seen with estrone sulfate. Five hours after injection into the PSI, biliary excretion was, in CVL 88.2% and in GF 81.7% and after injection into the DSI excretion was, in CVL 84.7% and in GF 83.6%. Absorption of estrone from the caeca of GF rats was apparently reduced (49.0% and 25.3% excreted in the bile of CVL and GF rats respectively). There was no significant difference in bile flow rate between CVL and GF rats. These results give unequivocal evidence of intact absorption of estrone sulfate from the small intestine of the rat. The rate of absorption is however very much reduced compared to the non-sulphated steroid. Estrone sulfate is not absorbed intact in the caecum but is hydrolysed by the gut microflora prior to absorption.