Somatomedins as regulators of proteoglycan synthesis.

Abstract

The pleiotypic effect of somatomedins on cells is well-known. This review deals with somatomedins (SMs) as regulators of proteoglycan (PG) synthesis. Once the mechanism of this role of SMs is understood, it can be used as a general macromolecular model for studying the effects of SMs on matrix components of connective tissues. The factors regulating PG production rate can be classified into two categories: 1. Intracellular factors which integrate the following: the genetic code, the synthetic enzymes and their organization, the availability of building block substances, various cell nutritional factors, and =-degrading enzymes. All these determine the basic rate of production. 2. Extracellular factors, including hormones secreted from glandular organs and tissuelocal agents with regulation ability. The hormonal factors may alter rates of PG production and generate differences in the product composition, reflecting changes in the individual’s developmental, physiological and/or pathological status. While hormones such as thyroxine which stimulates the rate and glucocorticosteroids which suppress the rate have been reported to regulate PG synthesis, the somatomedin (SM) family seems to play a key role in this regulation. The term somatomedin denotes the relation of a substance to somatotrophin (growth hormone (GH)), and its intermediary (mediator) role in transmitting the message of GH to the target or soma cells (e.g. fibroblasts, chondrocytes, osteocytes, etc.). At most, the SM family includes six members: SM-A, SM-B, SM-C, NSILA (non-suppressible insulinlike activity) I and 11, or in the new terminology IGF (insulin-like growth factor) I and 11, and MSA (multiplication stimulating activity). The SMs share certain common elements, and some of their characteristics are listed in Table I. In brief, the SMs are a group of low molecular weight polypeptides (ranging from 4000 to 8000 daltons) whose biological activity can be expressed as growth-promoting , insulin-like and mitogenic. The growth-promoting activity is assessed mainly by the effect of SM on the rate of matrix production: this is measured as the stimulation of sulfate incorporation into cartilage slices of various animals. The endocrine route of SMs begins with the hypothalamic secretions which cause the release of GH from the pituitary. This GH is believed to generate the synthesis of SMs, mainly in the liver and kidney, which then operate on their target cells via specific receptor sites on the cell membranes. PG synthesis (matrix production) has become over the years the indicator of the overall growth process of the bony framework and the level of SMs in blood has come to serve as the clinical anabolic index of serum content in growth factors.