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The secretion rate (SR) of oestradiol in rats at different stages of the oestrous cycle was determined by measuring the concentration of this hormone in ovarian vein plasma by a competitive protein binding method utilizing rabbit uterine cytosol. The plasma metabolic clearance rate (MCR_P) for oestradiol was determined in groups of rats of the same strain and housed under the same conditions by giving a single intravenous injection of tritiated oestradiol-17β and measuring the rate of disappearance of labelled hormone from the plasma. From the relationship SR = MCR_P x plasma concentration, predicted values for the plasma oestradiol concentration were obtained and shown to be close to those obtained by direct analysis of peripheral plasma.

The MCR_P for oestradiol was not greatly influenced by the stage of the oestrous cycle, the dose of oestradiol-17β injected, ovariectomy 18 h previously or by a sham-operation immediately before the injection of labelled hormone. The anaesthetic used did affect the MCR_P; the value for adult female rats injected under ether anaesthesia was about 970 ml/h but under Avertin anaesthesia clearance rates of about 1500 ml/h were obtained. Ligation of the bile duct acutely reduced the MCR_P but functional nephrectomy had no immediate effect. Sub-total hepatectomy 18 h previously reduced the MCR_P considerably. A small decrease in MCR_P was observed when the labelled hormone was administered in third trimester human pregnancy plasma and the MCR_P was lower in rats on Day 14 of pregnancy than in rats examined during the oestrous cycle.

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				D. R. Plowchalk and J. Teeguarden Development of a Physiologically Based Pharmacokinetic Model for Estradiol in Rats and Humans: A Biologically Motivated Quantitative Framework for Evaluating Responses to Estradiol and Other Endocrine-Active Compounds Toxicol. Sci., September 1, 2002; 69(1): 60 - 78. [Abstract] [Full Text] [PDF]