Estradiol release kinetics determine tissue response in ovariectomized rats

Endocrinology
Christiane OttoReinhold G Erben

Abstract

Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administratio...Continue Reading

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Citations

Jan 9, 2014·Expert Opinion on Drug Discovery·Pamela Cmd ZanniMárcia El Consolaro
Aug 21, 2013·Journal of Korean Medical Science·Kwi Young KangYeon Sik Hong
Dec 7, 2017·Nature Communications·Sivanandane SittadjodyEmmanuel C Opara
Sep 25, 2018·Journal of Neuroendocrinology·Isabelle CôtéPhilip J Scarpace

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