Estrogens do not affect whole-body protein metabolism in the prepubertal female.
The increase in bone mass, muscle bulk, and linear growth that occur during puberty are mediated, at least in part, through the action of sex steroids. By using infusions of nonradioactive tracers of leucine, we have recently shown a significant protein anabolic effect of testosterone in prepubertal boys. The present study was designed to determine whether estrogens can cause similar changes in protein metabolism in females. Seven prepubertal girls (Turner's syndrome, n = 6; hypogonadotropism, n = 1; mean age 12.2 +/- 0.3 yr) were studied. A 4-h infusion of L(-)[1-(13C)]leucine was given, and the isotopic enrichment of [13C]ketoisocaproic acid and 13CO2 were measured in plasma and in breath with use of gas chromatography/mass spectroscopy and an isotope ratio mass spectrometer, respectively. The reciprocal pool model was used for analysis of leucine kinetics. Subjects were then started on ethinyl estradiol orally (n = 5) or depot estradiol parenterally (n = 2). An identical study was repeated 4 weeks later. There were comparable changes in leucine kinetics in all girls studied, hence their data were grouped for analysis. After administration of ethinyl estradiol, there were insignificant changes in the rate of appearance of leucine, an index of proteolysis (+6% +/- 8%); leucine oxidation (-9% +/- 11%); and nonoxidative leucine disposal, an index of whole body protein synthesis (+10% +/- 8%). This is in sharp contrast to the changes found in boys studied similarly after treatment with testosterone (rate of appearance: 17 +/- 6%, P = .036; leucine oxidation -49 +/- 5%, P = 0.004; and nonoxidative leucine disposal +35 +/- 8%, P = 0.009). The lack of anabolic effect on whole-body protein in the girls reported here was observed despite significant increases in plasma insulin-like growth factor I concentrations during 4 h of sampling when comparing the 2 study days, similar to that of the prepubertal boys who were treated with testosterone. In summary, we observed that contrary to androgens, estrogens do not alter estimates of whole-body protein turnover and anabolism in prepubertal humans, despite significant increases in circulating insulin-like growth factor I concentrations. In conclusion, the impact of testosterone on protein metabolism seems to be a direct effect of androgens, independent of aromatization. These findings correlate with the significant differences in muscle bulk between the sexes as children go through puberty.
Mauras
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Division of Endocrinology, Nemours Children's Clinic, Jacksonville, Florida 32207, USA.
D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D002648:Child; D045166:Estradiol Congeners / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007006:Hypogonadism / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D007651:Keto Acids / Q000032:analysis; D007930:Leucine / Q000378:metabolism*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D011627:Puberty; D014424:Turner Syndrome / Q000378:metabolism*
D002247:Carbon Isotopes; D045166:Estradiol Congeners; D007651:Keto Acids; D011506:Proteins; D002245:Carbon Dioxide; D004997:Ethinyl Estradiol; C013082:alpha-ketoisocaproic acid; D007930:Leucine