androstane-3-17-diol-glucuronide and Puberty--Precocious

Premature pubarche (PP) appears to be a risk factor for the subsequent development of polycystic ovary syndrome (PCOS) during or after puberty. The clinical manifestations due to hyperandrogenism are influenced by androgen production, androgen metabolism, and androgen receptor activity. Glucuronidation by the UDP-glucuronyltransferase 2B (UGT2B) family of enzymes is one mechanism through which androgens are inactivated. Two variants differing by the amino acid at codon 85 have been described for UGT2B15, a member of this family. Both variants show similar substrate specificities. However, for the substrates alpha-androstanediol (alpha-diol) and dihydrotestosterone (DHT), the D85 variant has a lower Vmax than the Y85 variant. We compared the frequencies of these variants in 69 patients with PP, 46 adolescent girls with hyperandrogenism (HA), and 88 healthy controls to determine whether the frequency of the D85 variant was increased among patients with hyperandrogenism. Allele frequencies were comparable in children with PP, adolescent girls with HA, and healthy control subjects. Although D85 and Y85 appear to be common variants, we cannot exclude the possibility that the UGT2B15 gene represents a minor modifying locus.

Topics: Adolescent; Androstane-3,17-diol; Androstenedione; Child; Dihydrotestosterone; Female; Gene Frequency; Genotype; Glucuronosyltransferase; Heterozygote; Homozygote; Humans; Hyperandrogenism; Phenotype; Polycystic Ovary Syndrome; Puberty, Precocious; Sex Hormone-Binding Globulin; Testosterone

The aim was to study 3 alpha-androstanediol glucuronide (3AG) plasma levels and its relationship with 5-ene and 4-ene steroids in children with the benign form of precocious pubarche (precocious adrenarche). Sixty-five children with precocious adrenarche (PA), aged 3.6-8.2 yr (55 girls and 10 males) and 15 normal age-matched children were studied. We evaluated plasma androstenedione (A), dehydroepiandrosterone (DHA), its sulfate (DHA-S), testosterone (T), dihydrotestosterone (DHT), its glucuronide (DHTG), 3 alpha-androstanediol (3Ad) and its glucuronide (3AG) in all subjects. All androgens are expressed as mean +/- SD. We found significantly higher plasma levels not only in glandular androgens but also in peripheral androgens (A, 2.4 +/- 1.5 nM vs 0.79 +/- 0.46 nM, p < 0.001; DHA, 9.8 +/- 4.9 vs 2.7 +/- 0.76 ng/dl, p < 0.001; DHA-S, 3.4 +/- 2 microM vs 2.4 +/- 0.65 microM, p < 0.05; T, 0.74 +/- 0.5 nM vs 0.4 +/- 0.1 nM, p < 0.001; DHT, 0.36 +/- 0.13 nM vs 0.12 +/- 0.05 nM, p < 0.001; 3Ad, 0.13 +/- 0.1 nM vs 0.054 +/- 0.03 nM, p < 0.001; DHTG, 0.5 +/- 0.3 nM vs 0.26 +/- 0.09 nM p < 0.01). As far as the plasma 3AG levels are concerned we found significantly higher values in PA with respect to controls (1.17 +/- 0.7 nM vs 0.61 +/- 0.04 nM, p < 0.01), suggesting that 3AG may be considered a marker of skin androgen utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Androstane-3,17-diol; Androstenedione; Child; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Humans; Male; Puberty, Precocious; Testosterone

To investigate the role of adrenal androgens in 3 alpha-androstanediol glucuronide (3AG) production in childhood, we compared serum 3AG and androgen levels [dehydroepiandrosterone (DHEA), DHEA sulfate (DS), androstenedione (delta 4-A), and testosterone (T)] in 32 children with premature pubarche due to idiopathic premature adrenarche (IPA; n = 26), partial 21-hydroxylase deficiency (n = 2), or 3 beta-hydroxysteroid dehydrogenase deficiency (n = 4) with those in 36 normal prepubertal (18 males and 18 females) and 22 normal pubertal Tanner II-III subjects (10 males and 12 females). Serum 3AG (2.7 +/- 2.0 nmol/L) and all androgen concentrations in children with IPA were significantly higher (P less than 0.05-0.001) than those in normal prepubertal children (3AG, 0.8 +/- 0.5 nmol/L). Serum 3AG and androgen levels, except T, in all children with premature pubarche due to 21-hydroxylase deficiency or 3 beta-hydroxysteroid dehydrogenase deficiency were higher than those in the normal prepubertal children. Serum 3AG and all androgen levels in normal Tanner II-III male (3AG, 3.8 +/- 1.7 nmol/L) or female (3AG, 1.74 +/- 0.52 nmol/L) subjects were also significantly higher (P less than 0.05-0.001) than those in prepubertal children. Serum 3AG, DHEA, DS, and delta 4-A levels in children with IPA were similar to those in normal Tanner II-III females or males, but serum T in children with IPA (0.37 +/- 0.2 nmol/L) was significantly lower (P less than 0.05-0.001) than that in normal pubertal females (0.71 +/- 0.37 nmol/L) or males (4.5 +/- 2.6 nmol/L). In the combined group (n = 88), 3AG levels correlated better with serum DS (r = 0.7), DHEA (r = 0.6), and delta 4-A (r = 0.52), than with T (r = 0.31) levels. These data suggest that the weak adrenal androgens DS, DHEA, and delta 4-A contribute substantially to 3AG production in premature and normal pubarche.

Topics: 3-Hydroxysteroid Dehydrogenases; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Androgens; Androstane-3,17-diol; Androstenedione; Child; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Infant; Male; Puberty, Precocious; Testosterone