A specific radioimmunoassay for human IGFBP-2 was developed using a po
lyclonal antiserum directed against a partial sequence (hIGFBP-2(176-1
90)). The tracer was prepared by radioiodination of a [Tyr]0-hIGFBP-2(
176-190) derivative. The assay was used to study IGFBP-2 levels in num
erous clinical and experimental situations. There was little circadian
fluctuations of serum levels which showed a marked age-dependence wit
h high levels at birth and senescence and low levels during puberty. D
ecreased IGFBP-2 levels were present in untreated insulin-dependent di
abetes mellitus (IDDM), in acromegaly and during dexamethasone suppres
sion test. GH deficiency, fasting, IGF-I administration to patients wi
th GH receptor deficiency, hepatic failure and insulinomas caused a mo
derate increase of serum IGFBP-2. Markedly elevated levels were found
in chronic renal failure, non-islet cell tumour induced hypoglycemia a
nd leukaemias. The fact that all possible relationships between insuli
n secretion and IGFBP-2 levels could be identified suggests that insul
in is not a major regulator. In general, there was an inverse relation
ship with serum IGFBP-3 (except IDDM) and IGFBP-2 levels were high in
situations where free IGF-II should be expected to be high. The tentat
ive conclusion would therefore be that free IGF-II is a major regulato
r of circulating IGFBP-2.