Assessment of growth hormone (GH) axis in Turner's syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding activity, GH binding to IM9 cells, and GH response to pharmacological stimulation.

Abstract

The GH axis was studied in Turner's syndrome (TS) patients. Thirty-seven prepubertal TS patients and 42 normally growing girls (NGG; 5.5-16.3 yr old), of whom 13 were prepubertal, were studied by 24-h continuous blood withdrawal and provocative tests. The 24-h integrated concentrations of GH (IC-GH), FSH (IC-FSH), and insulin-like growth factor-I (IC-IGF-I) as well as the IC-IGF-I/IC-GH ratio were determined. An increase in IC-GH with age and progression of puberty was found in NGG, but not in TS. IC-GH in the NGG was significantly higher than that in age-matched TS patients. Estrogen replacement therapy normalized IC-GH levels in 6 TS patients in whom these levels were subnormal for age. A positive correlation between IC-GH and IC-FSH or IC-estradiol was found in NGG (r = 0.462; P less than 0.01), but not in TS patients. The IC-IGF-I/IC-GH ratio was significantly higher in the TS than in the NGG group. Serum GH-binding activity and serum GH binding to IM9 cells in the TS group did not differ from those in the normal group. We hypothesize that the growth retardation of TS results from a combination of insufficient GH secretion, mainly due to sex steroid deficiency, and an end-organ resistance to IGF-I. IGF-I receptor studies are needed to test this speculation about IGF-I resistance.

GH as a co-gonadotropin: the relevance of correlative changes in GH secretion and reproductive state

“…Ross et al (1985) observed normal GH secretory dynamics in girls with Turner's syndrome prior to 9 years of age, but significantly decreased mean 24-h GH levels, peak amplitudes and peak frequencies in girls between 9 and 20 years of age, compared with those in age-matched normal girls. Indeed, although an agerelated increase in GH pulse amplitude is observed in normal prepubertal girls, GH pulse amplitude in girls with Turner's syndrome remains the same or even declines (Massarano et al 1989, Zadik et al 1992. These results may, however, reflect age-related increases in obesity in girls with Turner's syndrome (Cianfarani et al 1994) rather than direct effects of estrogen, since GH-releasing hormone (GHRH)-induced GH secretion and obesity are inversely related in girls with Turner's syndrome (Lu et al 1991, Reiter et al 1991.…”

Plasma Growth Hormone-Binding Protein Activity, Insulin-like Growth Factor I, and Its Binding Protein Levels in Patients with Turner's Syndrome: Effect of Short- and Long-Term Recombinant Human Growth Hormone Administration

“…In fact, in these girls the GH secretory status has been found normal (6)(7)(8)(9) or impaired, mostly after the bone age of 10 y (6) or the chronologic age of 9 y (lo), when the growth delay is already manifest. In addition, the direct demonstration of an end-organ resistance to IGF-I has yet to be demonstrated, even if recent evidence supports this hypothesis (11).…”

Growth Hormone Bioactivity in Girls with Turner's Syndrome: Correlation with Insulin-like Growth Factor I1

“…( 17) have recently suggested that girls with Turner's syndrome lack tissue sensitivity to GH or IGF-I. However.…”

“…and expression of GH-binding protein ( 15,16). Previous studies estimating GH bioactivity by radioreceptor assays suggest that GH bioactivity is similar to that in normally growing girls ( 17,18). Also.…”

“…Also. because IGF-I concentrations are similar to those of normal girls, the endogenous GH in girls with Turner's syndrome is likely to support normal IGF-I production (17). Thus, this population of girls was likely to serve as a good model to determine whether GH bioactivity in serum determined in a metabolic assay would have a significant correlation with peptides involved in regulation of growth.…”