There is currently widespread interest in the IGFs (IGF-I and IGF-II) and their roles in the regulation of growth and differentiation of an ever increasing number of tissues are being reported. This selective review focused on the current state of our knowledge about the structure of mammalian IGFs and the multiple forms of mRNAs which arise from alternative splicing and promoter sites which arise from gene transcription. Current progress in the immunological measurement of the IGF is reviewed including different strategies for avoiding binding protein interference. The results of measurements of serum IGF-I and IGF-II in fetus and mother and at various stages of postnatal life are described. Existing knowledge of the concentration of these peptides in body fluids and tissues are considered. Last, an attempt is made to indicate circumstances in which the IGFs are exerting their actions in an autocrine/paracrine mode and when endocrine actions predominate. In the latter context it was concluded that an important role for GH action on skeletal tissues via hepatic production of IGF-I and endocrine action of IGF-I on growth cartilage is likely.

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Plasma growth hormone (GH), insulin, cortisol, and glucose were measured during sleep on 38 nights in eight young adults. Blood was drawn from an indwelling catheter at 30-min intervals; EEG and electrooculogram were recorded throughout the night. In seven subjects, a plasma GH peak (13-72 mug/ml) lasting 1.5-3.5 hr appeared with the onset of deep sleep. Smaller GH peaks (6-14 mug/ml) occasionally appeared during subsequent deep sleep phases. Peak GH secretion was delayed if the onset of sleep was delayed. Subjects who were awakened for 2-3 hr and allowed to return to sleep exhibited another peak of GH secretion (14-46 mjug/ml). Peak GH secretion was not correlated with changes in plasma glucose, insulin, and cortisol. The effects of 6-CNS-active drugs on sleep-related GH secretion were investigated. Imipramine (50 mg) completely abolished GH peaks in two of four subjects, whereas chlorpromazine (30 mg), phenobarbital (97 mg), diphenylhydantoin (90 mg), chlordiazepoxide (20 mg), and isocarboxazid (30 mg) .did not inhibit GH peaks. Altered hypothalamic activity associated with initiation of sleep results in a major peak of growth hormone secretion unrelated to hypoglycemia or changes in cortisol and insulin secretion.

We describe a case of recurrent hypoglycemia apparently caused by secretion of insulin-like growth factor II (IGF-II) by a leiomyosarcoma. A 67-year-old woman presented with recurrent severe hypoglycemia and a large mass in the thorax. During hypoglycemia, plasma cortisol was elevated, but insulin and growth hormone levels were low. After resection of a large leiomyosarcoma, the hypoglycemia resolved. After an eight-year remission, both the tumor and symptomatic hypoglycemia recurred. During a second operation a second large tumor was removed, with relief of the patient's hypoglycemia. The tumor contained high concentrations of IGF-II mRNA and 2100 ng of IGF-II immunoreactive peptide per gram. Filtration through a BioGel P-60 gel column established that 77 percent of the IGF-II was present as a larger molecule, demonstrating incomplete processing of the pro-IGF-II peptides. A similar fraction of high-molecular-weight IGF-II was present in the serum, indicating that the tumor was the chief source of IGF-II. The high-molecular-weight IGF-II found in both the tumor and serum was fully reactive with the IGF-II receptor. Radioimmunoassay showed that the concentrations of insulin-like growth factor I (IGF-I) in tumor and serum were low, suggesting feedback inhibition of growth hormone secretion by IGF-II. Eight months after reoperation, plasma concentrations of IGF-I and IGF-II were normal, and high-molecular-weight IGF-II was virtually undetectable. We conclude that the most likely cause of this patient's recurrent hypoglycemia was IGF-II produced by the leiomyosarcoma.

Previous measurements of somatomedins (Sms) and insulin-like growth factors (IGFs) in maternal and fetal serum have yielded contradictory results. We have, therefore, measured maternal, fetal, and neonatal rat serum with two highly specific assays: 1) IGF-I/Sm-C RiA and 2) a highly specific IGF-II/rat placental membrane radioreceptor assay (RRA). In addition, we have made measurements with a less specific multiplication-stimulating activity (MSA)-rat placental membrane RRA. To avoid possible serious artifacts created by Sm-binding proteins, preliminary acid-ethanol extraction of serum was performed. Results are expressed in terms of a reference human serum with an assigned potency of 1 U/ml. Maternal RIA IGF-I fluctuated between 1.1-1.4 U/ml from the 17th day of pregnancy to the 25th day after delivery (nonpregnant rat serum pool, 1.25 +/- 0.22 U/ml). On day 21 of gestation, fetal serum radioimmunoassayable IGF-I was 1.03 +/- 0.03 U/ml. After birth, radioimmunoassayable IGF-I fell and reached .19 +/- 0.03 U/ml at 18 days of age, but rose to 0.71 +/- 0.04 U/ml at 25 days of age. At term, maternal radioreceptor assayable IGF-II was 2.18 +/- 0.27 U/ml (nonpregnant female pool, 1.4 +/- 0.12). By the 25th postpartum day, radioreceptor assayable IGF-II was 1.39 +/- 0.12 U/ml. Radioreceptor assayable IGF-II in fetal serum on day 19 was 3.26 +/- 0.48 U/ml and rose to 5.37 +/- 0.66 U/ml on the day of delivery. A further rise to 8.92 +/- 1.03 occurred on day 5. A subsequent fall to 2.41 +/- 0.05 U/ml was observed on day 25. The patterns of results of the MSA RRA in fetal and neonatal rat serum were similar to that obtained with the IGF-II RRA. We now conclude that radioimmunoassayable IGF-I is present in higher concentrations than previously reported in term fetal rat serum and that radioreceptor assayable IGF-II is selectively elevated in rat fetal and neonatal life and may have unique metabolic and growth-promoting significance.U