Prolonged activation of the hypothalamus-pituitary-gonadal axis in a child with X-linked adrenal hypoplasia congenita.
X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder of the human adrenal cortex that is caused by a mutation of the DAX-1 gene, a member of the nuclear hormone receptor superfamily. Hypogonadotrophic hypogonadism is frequently associated with this disease and the DAX-1 mutation is known to impair gonadotrophin production by acting at both the hypothalamic and pituitary levels. However, three recent studies reported that the hypothalamic-pituitary-gonadal axis was active in six infants with AHC, suggesting that a difference exists in the central regulation of hypothalamic-pituitary-gonadal activity between infant boys and pubertal boys. To determine the effect of the DAX-1 gene mutation on the axis in early childhood, we measured testosterone, LH, and FSH and performed LH-releasing hormone tests on a boy with AHC from birth to 3 years of age. Surprisingly, our findings showed that the axis was active from the infantile period to 3 years of age. This delayed initiation of the prepubertal pause, or prolonged activation of the axis, indicates that the DAX-1 gene is related to the control mechanism of the prepubertal restraint of gonadotrophin secretion.
Department of Paediatrics, Akita University School of Medicine, Japan.
I
I
Takahashi
T
T
Takahashi
Y
Y
Shoji
G
G
Takada
D000309:Adrenal Insufficiency / Q000151:congenital / Q000235:genetics / Q000503:physiopathology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D008040:Genetic Linkage; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007231:Infant, Newborn; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D013737:Testis / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood; D014960:X Chromosome
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone