Order of magnitude differences between methods for maintaining physiological 17beta-oestradiol concentrations in ovariectomized rats.
The use of animal models, especially the rat, is crucial for elucidating the biological effects and mechanisms of the widely used hormone 17beta-oestradiol. Unfortunately, there is a lack of consensus on optimal means of obtaining and maintaining physiological 17beta-oestradiol concentrations in plasma and this may be the reason for the varying results in several studies, including the disagreement on whether 17beta-oestradiol is neuroprotective or not. Very few studies have been devoted to investigating the characteristics and biological relevance of different methods of 17beta-oestradiol administration. We therefore ovariectomized 75 Sprague-Dawley rats and, following a 2-week washout period, administered 17beta-oestradiol using three different methods; daily injections (10 microg 17beta-oestradiol/kg), slow-release pellets (0.25 mg 60 day-release pellets, 0.10 mg 90 day-release pellets) and silastic capsules (with/without washout periods) (silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with 20 mm columns of 180 microg 17beta-oestradiol/mL sesame oil). A further 45 animals were used as ovariectomized and native controls studied in different parts of the oestrous cycle. Silastic capsules produced concentrations of 17beta-oestradiol within the physiological range 4-5 weeks independently of whether a prior washout period was included or not. The slow-release pellets, irrespective of dose or release period, resulted in initial concentrations an order of magnitude above physiological concentrations during the first 2 weeks followed by a substantial decrease. Daily injections resulted in increasing 17beta-oestradiol concentrations, but within physiological levels. Silastic capsules are conveniently manufactured and used and are superior to pellets and injections in reliably producing long-term 17beta-oestradiol concentrations within the physiological range.
Ström
Jakob O
JO
Department of Clinical Chemistry, Institute of Clinical and Experimental Medicine, University Hospital, Linköping, Sweden.
Theodorsson
Elvar
E
Theodorsson
Annette
A
D000818:Animals; D002214:Capsules; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood* / Q000494:pharmacology; D005260:Female; D007267:Injections; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D002214:Capsules; D003692:Delayed-Action Preparations; D004958:Estradiol