Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome (SRY)-positive 46,XX karyotypes.
BACKGROUND
Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles.


OBJECTIVE
The aim of the study was to evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I, and IGF binding protein (IGFBP)-3.


METHODS
The study was conducted at an outpatient clinic, Copenhagen University Hospital.


METHODS
Participants included 86 47,XXY males, 14 46,XX-males, and nine 47,XYY.


METHODS
Standing and sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured.


RESULTS
In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal.


CONCLUSIONS
We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth-related genes.
Aksglaede
Lise
L
University Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. lise.aksglaede@rh.hosp.dk
Skakkebaek
Niels E
NE
Juul
Anders
A
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D041322:Chromosomes, Human, Y; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006128:Growth / Q000235:genetics / Q000502:physiology; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007713:Klinefelter Syndrome / Q000097:blood* / Q000235:genetics*; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D012729:Sex Chromosome Aberrations; D013739:Testosterone / Q000097:blood; D014997:XYY Karyotype / Q000097:blood* / Q000235:genetics*
D018972:Insulin-Like Growth Factor Binding Protein 3; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone