We have validated a method for extracting and measuring the tissue content of somatomedin C (Sm-C)/insulin-like growth factor I (IGF-I), a growth-hormone-dependent, growth-promoting peptide. The Sm-C content of tissue extracts was strongly growth-hormone dependent because most of the tissues studied from hypophysectomized rats contained significantly less Sm-C than normal tissues. The intraperitoneal administration of ovine growth hormone (oGH) to hypophysectomized rats caused tissue extractable Sm-C to increase in kidney, liver, lung, heart, and testes. Tissue Sm-C responses to oGH were maximal after 12 hr, 6 hr before the maximal increment in serum. In liver and lung, the tissue Sm-C response to various doses of oGH fit linear regression models, and the doses of oGH needed to increase the Sm-C are in the range of those required to increase protein synthesis. Although these results do not exclude the possibility that the somatomedins act by hormone-like endocrine mechanisms, they add support to the concept that these peptides act through autocrine or paracrine mechanisms, being produced at multiple sites and acting at or near their sites of production.There is now evidence that somatomedins, traditionally considered to originate in the liver, are synthesized at multiple sites (1, 2). Using explant cultures, we have observed that a variety of fetal mouse organs elaborate immunoreactive somatomedin C (Sm-C) into medium (3). Furthermore, it has been shown that Sm-C/insulin-like growth factor I (IGF-I) is synthesized by cultured human and rat fibroblasts (4-6). These findings suggest that the somatomedins might act through paracrine or autocrine mechanisms, having their biologic actions at or near their sites of origin. If such mechanisms are operative, alterations in somatomedin physiology may be better reflected by estimation of tissue concentrations than by measurement of concentrations in blood. Using a newly devised method for extraction of Sm-C, we addressed these possibilities by comparing tissue concentrations of immunoreactive Sm-C in normal rats and their hypophysectomized littermates. In addition, we assessed the tissue Sm-C response to the administration of growth hormone in hypophysectomized rats.MATERIALS AND METHODS Animals. Hypophysectomized male Sprague-Dawley rats and their normal littermates were purchased from ZivicMiller Labs (Allison Park, PA). Hypophysectomy was carried out when the animals weighed =100 g. Animals were fed standard laboratory chow ad lib, and provided water, each liter of which contained 2.03 g of NaCl, 83.3 mg of KCl, 2.1 mg of CaCl, 16.7 mg of MgCl, and 50 g of sucrose. Two sets of rats were used for the experiments. At the time of sacrifice, 48-50 days of age and 20 days after operation, the hypophysectomized groups weighed 100.4 ± 9.8 g (mean ± SD; n = 68) and 107.2 ± 8.2 g (n = 25). The mean weights for the two groups of normal rats were 251.6 ± 17.7 g (n = 7) and 263.8 ± 18.6 g (n = 6). Completeness of hypophysectomy was verified by direct examination of the sel...

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In kidney tissue extracts, we observed elevated somatomedin-C (SmC) tissue concentrations in the kidney remaining after nephrectomy compared to those in the kidney removed at surgery or kidneys from sham-operated animals. In hypophysectomized animals, we observed a response of the same magnitude, but from significantly lowered basal SmC concentrations. In neither case did nephrectomy affect SmC levels in serum or other tissues studied (liver and lung). The increased tissue levels of SmC in the regenerating kidney, with a return to baseline levels within 30 days, along with the absence of elevated serum levels suggest a local role for this mitogen in organ growth.

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