Somatomedin-C Levels in Children and Adolescents with Gonadal Dysgenesis: Differences from Age-Matched Normal Females and Effect of Chronic Estrogen Replacement Therapy*

Abstract

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 agematched normal girls. Between ages 4–9 yr, patients with gonadal dysgenesis had Sm-C levels similar to those in the agematched 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-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 < 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.