The factors responsible for the elevation of circulating
somatomedin-C/
insulin-like growth factor I (Sm-C) during normal pubertal development are uncertain. To assess the role of ovarian
estrogen secretion during puberty, we examined the effect of
estrogen deficiency due to primary
hypogonadism on Sm-C levels in late childhood and early adolescence. The concentration of immunoreactive Sm-C was measured in 36 untreated patients with
gonadal dysgenesis (age, 4-16 yr); results were compared with the pattern of change in Sm-C in 153 age-matched normal girls. Between ages 4-9 yr, patients with
gonadal dysgenesis had Sm-C levels similar to those in the age-matched normal subjects. In contrast to the normal girls, Sm-C levels in patients with
gonadal dysgenesis did not rise after 10 yr of age and were significantly lower than those in normal girls at 11-16 yr of age. The effect of low dose
estrogen therapy was assessed in eight patients with
Turner's syndrome. Their Sm-C levels were measured before and during 2-12 months of treatment with
ethinyl estradiol (90-220 ng/kg X day). The mean Sm-C concentration rose from 0.72 +/- 0.06 U/ml (+/- SEM) before treatment to 1.17 +/- 0.17 U/ml during
estrogen treatment (P less than 0.04). In three patients who had a similar increase in Sm-C during
estrogen treatment, interruption of
therapy was associated with a fall in Sm-C concentrations; when
estrogen therapy was reinstituted in two of these patients, Sm-C levels rose again. These results suggest that increasing endogenous
estrogen production is a major determinant of the rise of circulating Sm-C that occurs during pubertal development in normal girls. Chronic
estrogen deficiency, as in untreated patients with
gonadal dysgenesis, is associated with failure to manifest the elevation of Sm-C that occurs during normal puberty.