title: Cortisol succinate is slowly hydrolysed in organ cultures of porcine articular tissues and is not equivalent to cortisol.
abstract: The pro-drug cortisol succinate is frequently used as a substitute for cortisol in organ cultures. We found, however, that in Dulbecco's modified Eagle's medium the time taken for the ester to undergo 50 per cent hydrolysis (t1/2) to cortisol was 75 h. When 15 per cent heat-inactivated normal rabbit serum was present t1/2 decreased to 47 h, but the rate of hydrolysis was not further increased in the presence of porcine articular cartilage or minced synovial tissue. When frozen and thawed synovium was present t1/2 decreased to 33 h, presumably due to the release of carboxyl-esterases from the disrupted cells. The level of tetrahydrocortisol was low in all of the cultures. The slow hydrolysis of cortisol succinate resulted in the exposure of the tissues to undesirable fluctuations in the concentration of active hormone, which decreased to low levels at each medium change. Thus, in co-cultures of porcine synovium and articular cartilage, cortisol had a greater inhibitory effect than cortisol succinate on the breakdown of cartilage matrix caused by synovial tissue.
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D009924:Organ Culture Techniques; D013552:Swine
chemical_list: C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone