Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.

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Vigersky RA, Easley RB, Loriaux DL

Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.

J Clin Endocrinol Metab. 1976 Jul;43(1):1-9.

PubMed ID

947929 [ View in PubMed

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Abstract

Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Fluoxymesterone	Sex hormone-binding globulin	Protein	Humans	Unknown	Antagonist	Details