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Order of magnitude differences between methods for maintaining physiological 17beta-oestradiol concentrations in ovariectomized rats
Linköping University Hospital, Linköping, Sweden.ORCID iD: 0000-0002-6681-0546
Linköping University Hospital, Linköping, Sweden.
Linköping University Hospital, Linköping, Sweden.
2008 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 8, 814-822 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oslo, Norway: Taylor & Francis, 2008. Vol. 68, no 8, 814-822 p.
Keyword [en]
Injections, oestrogens, pharmacokinetics, silastic capsules, slow-release pellets, washout
National Category
Medical and Health Sciences Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-48114DOI: 10.1080/00365510802409703ISI: 000263221000022PubMedID: 18821130Scopus ID: 2-s2.0-57349170348OAI: oai:DiVA.org:oru-48114DiVA: diva2:901439
Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2017-10-17Bibliographically approved

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CiteExportLink to record
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