ABSTRACT
Equilibrium concentrations of oestrone (OE1) and 17β-oestradiol (OE2) metabolites in rat tissues were investigated by means of long-term infusions with varying amounts of labelled hormones.
3 hour-infusions were found sufficient to allow an equilibrium to be established between concentrations of metabolites in the plasma, liver, uterus, adrenals, fat and striated muscle and the infusion rate. In all these tissues, except the uterus, the equilibrium concentration was directly proportional to the rate of infusion. (The »concentration index«, i. e. the concentration per unit rate of infusion was constant). Hence, the results could be directly interpreted on a physiological basis. OE1 and OE2 were the major metabolites in all the tissues investigated, accounting for 47 to 78% of the total radioactivity in the plasma, 82 to 102% in the uterus, 40 to 48% in the liver, 80 to 120% in the adrenals, 53 to 85% in the adipose tissue and 66 to 93% in the muscle. Other fractions consisted of conjugates, mostly in the liver: 11 to 23% and in the plasma: 15 to%, of polar metabolites, mostly in the liver: 19% to 33%, or of non-polar metabolites, mostly in the adipose tissue: 5 to 17% and in the adrenals: 2 to 12%. The infused hormone was always predominant in all the tissues investigated except in the liver where the OE1/OE2 ratio was about 10, in either type of infusions. Hence, extensive interconversion between OE1 and OE2 was found to occur in that tissue. OE1 was taken up to a higher level than OE2 in the adipose tissue, whereas the reverse situation occurred in the uterus. In the latter tissue, the uptake was higher towards the end as compared to the early period of the cycle.
A »molar concentration index« (i. e. molar concentration per unit rate of infusion) of the infused hormone (either OE1 or OE2) was calculated. It ranged from 0.7 to 7 × 10−11 m/kg/ng/h, depending on the tissue investigated. Hence the OE2 concentration in these tissues under physiological conditions is not likely to exceed 10−9 m/kg.
The results are discussed with regard to the mechanism of hormone uptake in the tissues and the metabolism of the hormone, as assessed by urinary analysis.