Effect of gonadectomy on growth hormone, IGF-I and sex steroids in children with complete and incomplete androgen insensitivity

Abstract

IGF-I, testosterone and estradiol levels were evaluated in 8 girls with androgen insensitivity immediately before and from 1 to 3 months after bilateral gonadectomy. In 6 patients GH secretion was evaluated before and after gonadectomy by means of an arginine test and in 3 a sleep test was also performed. Mean IGF-I level before surgery was significantly higher than that of normal controls (2850 \ m=+-\ 1230 vs 1680 \ m=+-\1040 U/l, p < 0.025). After gonadectomy a significant decrease was evident for testosterone, estradiol and IGF-I levels. A positive correlation between IGF-I and estradiol levels was present before surgery (p < 0.005). The presence of a correlation with estradiol, but not with testosterone, and the knowledge that this syndrome is due to an insensitivity to androgens, but not to estradiol, support the hypothesis that the estradiol level is the major determinant for the control of IGF-I values in these patients. After gonadectomy, a substantial decrease of the 12-h nocturnal GH secretion was evident. Comparison of the nocturnal GH levels before surgery of the 3 patients with those of normal subjects of the same age showed hormonal values higher than 1 sd over the mean values of control subjects. Even if the number of patients studied is too small to draw any definitive conclusion, these data may suggest that sex hormones play a role in the control of IGF-I levels, a function which seems to be mediated through GH secretion.Plasma IGF-I level increase strikingly during pub¬ erty and this change is concomitant with the rise in sex hormone concentrations (1,2). Some investiga¬ tors have described an increase in GH secretion in subjects with normal or precocious puberty (3-7) and a decrease in IGF-I and GH values in children with central precocious puberty after suppression of gonadal sex steroid secretion by GnRH anal¬ ogues (6, 7). Exogenous testosterone administration in¬ creases 24-h GH secretion in boys with short stature and/or delayed sexual development (8) and induces a significantly greater IGF-I rise in prepubertal GH-suflicient than in prepubertal GHdeficient patients (9).Although these data indicate a relationship be¬ tween sex steroid and IGF-I levels, the effects of sex hormones on spontaneous GH secretion is still controversial. Whether the pubertal increase in IGF-I is mediated through enhanced GH secretion is still under discussion (8,10-15).Children submitted to castration provide a good model to assess the role of sex steroids on IGF-I and GH secretion. This study was designed to evaluate the effects of gonadectomy on IGF-I and GH production in a group of 8 children with an¬ drogen insensitivity. Patients and MethodsWe studied 8 girls with a chronological age ranging from 10.5 to 13.2 years (mean ± si) 11.6 ± 1.02) and a bone age from 8.2 to 13.0 years (10.9 ± 2.07).The clinical picture (presence of palpable testes in the labia majora or in the inguinal canal, normal external genitalia, normal male kariotype 46,XY) and the hor-

Mutational Analysis of Androgen Receptor (AR) Gene in 46, XY Patients with Ambiguous Genitalia and Normal Testosterone Secretion: Endocrinological Characteristics of Three Patients with AR Gene Mutations

“…Endocrinological data for partially virilized patients with AR abnormality in prepubertal children after the age of one year are limited. Although basal levels of T and LH were reported to be normal in partially virilized patients with possible AR dysfunction during the prepubertal period after the age of one (1, 11, 12), our data showed that basal T levels were higher than the undetectable limit. Ascertainment bias could not be denied, because one of our inclusion criteria was detectable basal T level in one patient of this study.…”

“…Endocrinological data of partially virilized children with AR dysfunction at the prepubertal stage are also limited. Normal basal levels of both T and LH (1, 11, 12) have been reported. Two patients in this study (patients 25 and 26) were reported with their endocrinological data, previously (13, 14), and these cases remind us that T after the hCG test and LH after the GnRH test are relatively elevated.…”

Estrogens and Androgens in Skeletal Physiology and Pathophysiology

“…The main sex difference is the pattern of GH spikes, with males exhibiting a more ordered secretion than females, both before and after puberty (528). Sex steroids affect GH secretion both in puberty and adulthood (104,441). Additionally, the perinatal T peak determines malepattern pituitary GH secretion as well as sex-specific hepatic steroid metabolism via imprinting mechanisms (234).…”