Abstract
ABSTRACT The metabolism of [4-14C] oestrone has been investigated in the microsomal fractions of liver of euthyroid, hypothyroid, hyperthyroid and thyrotoxic rats; the formation of the ether soluble, water soluble and protein-bound fractions was studied. It was found that the biotransformation of oestrone depended upon the function of the thyroid. Oestrone was metabolised to a higher degree in hyperthyroid rats, but to a lesser degree in thyrotoxic and hypothyroid rats. The behaviour of the ether soluble, water soluble and protein-bound fractions exhibited marked differences between the various groups of animals studied. In hyperthyroid and thyrotoxic rats, the metabolism of the ether soluble fractions was accelerated, and the formation of the protein-bound fractions was faster and more extensive than in euthyroid rats; in hypothyroid animals, only small differences in the protein-bound fraction were observed. In all four groups of animals, the amounts of the water soluble fractions were approximately the same. After incubation of oestrone with the microsomal fractions of liver of euthyroid, hyperthyroid, thyrotoxic as well as hypothyroid rats the following metabolites were identified in the ether soluble fractions: 6α-, 6β-and 7α-hydroxyoestrone, 6α- 6β- and 7α-hydroxy-17β-oestradiol, 16α-hydroxyoestrone, oestriol and 17β-oestradiol. The amounts of metabolites formed depended upon the functional state of the thyroid. No increased 16α-hydroxylation of oestrone was noticed in the ether soluble fraction of hypothyroid rats, whereas in the hypothyroid human an increase in the excretion of oestriol in urine as compared to normal subjects is observed (Brown & Strong 1965; Fishman et al. 1965). This discrepancy may be explained by species differences, by an extrahepatic metabolism of oestrone or by differences in the conjugation of oestriol. To obtain more information about the interrelationship between thyroid function and the metabolism of oestrone in liver, further investigations of the chemical nature of the water soluble and the proteinbound metabolites of oestrone are necessary.
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