[Effect of the GH-PRL superfamily on circulating plasma insulin-like growth factor-1]

To elucidate the effects of growth hormone (GH), prolactin (PRL), and human placental lactogen (hPL) on the regulation of insulin-like growth factor (IGF-1), we compared plasma IGF-1 levels, the pattern of circulating IGF-1-IGF-binding protein complexes (IGF-1 complexes), and unsaturated binding protein (USBP) levels among 1) naturally growing Wistar rats at several developmental stages, 2) rats subcutaneously administered GH, and 3) hypophysectomized rats treated with each of the three hormones. We further evaluated the in vitro secretion of IGF-1 by primary cultured rat hepatocytes, following exposure to the hormones singly or in combination. Plasma IGF-1 and USBP levels were determined by radioimmunoassay and competitive radioassay, respectively. IGF-1 complexes were separated from plasma and culture medium by Sephadex G150 and HPLC gel-chromatography, respectively. The results were as follows. 1) In naturally growing rats, plasma IGF levels were low during fetal life and after birth until 28 days of age, and thereafter increased rapidly to reach an adult level by 35 days. At 35 days, the molecular distribution of IGF-1 switched from an infantile pattern (only 40Kd IGF-1 complex) to an adult form (IGF-1 complexes with both 40Kd and 150Kd proteins). In addition, 150Kd USBP became detectable after 28 days. 2) Administration of GH for 3 days to 13-day-old rats induced 150Kd USBP 9 days earlier than in controls, while plasma IGF-1 levels remained comparable throughout the period examined. 3) In the hypophysectomized rats, plasma IGF-1 levels decreased to approximately one fifth of those in untreated rats, accompanied by the disappearance of 150Kd USBP and 150Kd IGF-1 complex. However, when GH (but not PRL or hPL) was continuously administered for 72 hrs, plasma IGF-1 levels and the circulating profile of IGF-1 complexes were nearly restored to those in control rats. 4) Addition of GH (but not PRL) to the culture medium caused hepatocytes to secrete IGF-1, consisting of only the 40Kd IGF-1 complex. This effect was blocked by the simultaneous addition of hPL with GH. These findings indicate that, of the hormones analyzed, GH is the most important regulator of the plasma IGF-1 concentration and circulating complex forms during the developmental periods in rats, as is also thought to be the case in humans.