Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism.
BACKGROUND
The Leydig cell hormone insulin-like factor 3 (INSL3) is important for testicular descent. Currently INSL3 levels in cord blood, in serum throughout childhood, and in relation to congenital cryptorchidism are unknown.


OBJECTIVE
The objective of the study was to characterize INSL3 levels in cord blood during the postnatal activation of the hypothalamic-pituitary-gonadal axis and in later childhood in normal boys and girls and cryptorchid boys.


METHODS
Serum from 267 3-month-old boys of a prospective study with standardized cryptorchidism classification was analyzed for INSL3 (of these, 99 also had cord blood samples). Testicular position was known in 151 controls and 54 transiently cryptorchid and 62 persistently cryptorchid subjects. Eight infant girls, 26 boys (4.1-10.1 yr), and 13 girls (3.7-8.7 yr) were also included.


METHODS
INSL3, age, testicular position, LH, and testosterone were measured.


RESULTS
INSL3 levels were significantly higher (P < 0.001) in cord blood and 3-month-old boys as compared with older prepubertal boys. At 3 months of age, INSL3 correlated significantly with LH in healthy boys. Cord blood INSL3 was significantly reduced in persistently cryptorchid boys (P = 0.001), and 3-month-old persistently cryptorchid boys had a significantly increased LH to INSL3 ratio (P = 0.014). INSL3 was unmeasurable in girls at all ages.


CONCLUSIONS
In boys, early postnatal INSL3 is markedly higher as compared with later childhood, presumably because it is stimulated by the transient postnatal LH peak. INSL3 was unmeasurable in girls at all ages. Reduced cord blood INSL3 and an increased LH to INSL3 ratio at 3 months of age in persistently cryptorchid boys suggest impaired Leydig cell function in cryptorchid boys already in the perinatal period.
Bay
Katrine
K
University Department of Growth and Reproduction, Rigshospitalet, GR 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. katrine.bay@rh.regionh.dk
Virtanen
Helena E
HE
Hartung
Stefan
S
Ivell
Richard
R
Main
Katharina M
KM
Skakkebaek
Niels E
NE
Andersson
Anna-Maria
AM
Toppari
Jorma
J
D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003456:Cryptorchidism / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood*; D007985:Leydig Cells / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011506:Proteins; D013737:Testis / Q000166:cytology / Q000502:physiology*; D013739:Testosterone / Q000097:blood
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D013739:Testosterone; D007986:Luteinizing Hormone