Effects of exogenous thyroxine on C-2 and C-16 alpha hydroxylations of estradiol in humans.
Thyroid dysfunction in humans is known to alter the excretory pattern of estrogen metabolites, suggesting that thyroid hormone directly influences the oxidative metabolism of estradiol. We examined the extent to which a brief period of hyperthyroidism specifically affected estradiol hydroxylation at C-2 and C-16 alpha, the two primary and competing sites of estrogen oxidation, using an in vivo radiometric assay in healthy male volunteers. Hydroxylation at C-2 was increased by a 2-week course of thyroxine (4.3 micrograms/kg/d) from 29.9% +/- 2.6% to 35.9% +/- 3.1% (P = 0.04), while 16 alpha-hydroxylation was unchanged (10.3% +/- 0.8% versus 9.3% +/- 0.5%). The greater extent of oxidation at C-2 was evidenced by a twofold increase in the urinary excretion of 2-hydroxyestrone (2.88 +/- 0.32 versus 5.30 +/- 0.85 micrograms/g creatinine), while the excreted products of 16 alpha-hydroxylation were unchanged. At the same time, significant reductions in total cholesterol (173.8 +/- 7.9 versus 139.4 +/- 8.9 mg/dl), low-density lipoprotein cholesterol (110.0 +/- 5.3 versus 83.8 +/- 7.7 mg/dl), and apolipoprotein B (68.2 +/- 3.3 versus 53.1 +/- 3.6 mg/dl) were observed. Serum levels of estrone, estradiol, sex hormone-binding globulin, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, and apolipoprotein A-I were not significantly affected. This study adds to the growing evidence that catechol estrogen production in humans is more readily regulated than 16 alpha-hydroxylation, which is relatively refractory to treatment.
Michnovicz
J J
JJ
Laboratory of Biochemical Endocrinology, Rockefeller University Hospital, New York, New York.
Galbraith
R A
RA
D000328:Adult; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000652:urine; D006728:Hormones / Q000097:blood; D006801:Humans; D006900:Hydroxylation; D008055:Lipids / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D011863:Radioimmunoassay; D011874:Radiometry; D039181:Steroid 16-alpha-Hydroxylase; D013974:Thyroxine / Q000494:pharmacology*
D004967:Estrogens; D006728:Hormones; D008055:Lipids; D004958:Estradiol; D039181:Steroid 16-alpha-Hydroxylase; D013974:Thyroxine