The substrate specificity of the catechol-O-methyltransferase, purified from human liver 380-fold, has been tested with a variety of compounds. Cateehol estrogens, as well as cateehol amines are methylated to their corresponding monomethyl ethers. The relation of the rates of methylation of cateehol estrogens and cateehol amines depended on enzyme and substrate concentration; under standard assay conditions, 2-hydroxy-17P-estradiol was the preferred substrate for the enzyme, as compared with epinephrine and other catechols tested. K m -values for 2-hydroxy-17P-estradiol were 15 M*M, for 2-hydroxy-estrone 20 M-M, for 2-hydroxy-estriol 25 M^M and for 4-hydroxy-estrone 20 M-M. For epinephrine and norepinephrine, K m -values of 300 M-M and 200 \IM, respectively, were obtained. The ratio of formation of the isomeric monomethyl ethers of cateehol estrogens varied between 1.3 and 95, depending on the substrate incubated. On the basis of kinetic studies with different enzyme preparations, different inhibitors and different concentrations of the substrates, it is concluded that both cateehol estrogens and cateehol amines are methylated by the same catechol-O-methyltransferase. The enzymic methylation of epinephrine was inhibited competitively by 2-and 4-hydroxylated estrogens; the K,-values were 7.0 M-M for 2-hydroxy-17P-estradiol, 8.5 M-M for 2-hydroxy-estrone, 12.2 M-M for 2-hydroxy-estriol, 50 M-M for 4-hydroxy-estrone and, for comparison, 154 M-M for the addition of norepinephrine. A non-competitive inhibition was observed with the corresponding isomeric monomethyl ethers. The extent of inhibition not only depended on the relative concentrations of substrates and inhibitors, but also on the concentrations of MgClo, 5-adenosylmethionine and enzyme.The results reported here indicate that the enzymic methylation and biological inactivation of neurotransmitters is strongly inhibited by 2-hydroxy-estrogens. These findings are of possible clinical relevance with respect to the regulation of blood pressure under normal and pathological conditions. (/ Clin Endocr 34: 736, 1972)

Abstract. Under the protection of ascorbic acid a 4-hydroxyoestrone-bovine serum albumin conjugate was prepared containing intact 4-hydroxyoestrone as determined by gas chromatography-mass spectrometry. Using this antigen, antibodies with high affinity and specificity for 4-hydroxyoestrone were raised in rabbits. An assay procedure for the determination of 4-hydroxyoestrone in human urine and the assessment of its reliability are described. The following urinary excretion rates were found: male children 0.29 μg/24 h, female children 0.35 μg/24 h, men (20–40 years) 1.6 μg/24 h, men (>50 years) 1.8 μg/24 h, women, follic. 2.0 μg/24 h, pre-ov. 5.3 μg/24 h, luteal 2.4 μg/24 h, women, pregnant, first trim. 30.0 μg/24 h, second trim. 64.0 μg/24 h, third trim. 48.0 μg/24 h, women, post-men. 1.5 μg/24 h. Thus the amounts of 4-hydroxyoestrone excreted in human urine are about 1/3 to 1/10 of those of 2-hydroxyoestrone. During the menstrual cycle the excretion rates of 4-hydroxyoestrone are in the same order of magnitude as those of oestradiol and show a clear-cut pre-ovulatory peak.

A study was undertaken to determine the effect on the rate of deposition of dentin when high levels of adrenal glucocorticoid hormone are administered to rats. The results indicate that in the hypercorticoid rat, despite an increased eruption rate and a reduced width of incisor wall, no alteration occurs in the rate of dentin formation.

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