DISTRIBUTION OF INSULIN-LIKE GROWTH FACTORS AND IGF BINDING PROTEINS DURING PREGNANCY IN THE RABBIT. † 1326

Abstract

We have previously demonstrated a 16,000-fold increase in maternal insulin-like growth factor (IGF)-II with parallel changes in IGF binding proteins (IGFBPs) by mid-late gestation in the rabbit. The purpose of the present study was to characterize the distribution of the IGF-I, -II and IGFBPs and to identify the site(s) of production of these peptides in pregnant rabbits. In serum from nonpregnant rabbits and from does up to 24 days of gestation (term = 31-32 days), total circulating IGF was predominately associated with the 150 kDA ternary complex by neutral size-exclusion chromatography, but at day 30 both IGFs were carried by the smaller IGFBPs. The distribution of serum IGFBPs at day 24 revealed a substantial increase in the IGFBP-3 doublet and a broad 30kDa IGFBP eluting in fractions of the 150 kDa region, yet at day 30, all IGFBPs were substantially decreased. Although there was no IGFBP-3 proteolytic activity detected at day 24, but there was significant proteolytic activity at day 30, possible explaining the decreased IGFBPs. Northern blot analysis demonstrated that IGF-II and IGFBP-3 are produced by the placenta, while maternal liver is the source of IGFBP-1. These data suggest that the placenta is the key modulator of the IGF axis in the pregnant rabbit. (Supported by NIH CA-58110 and HL-44941, Dr. Labarta received scholarship 94/5373 from Fondo de Investigation Sanitaria, Spain).