Enhancement of somatomedin titers of normal and hypopituitary sera by addition of L-triiodothyronone in vitro at physiological concentrations.

Abstract

Somatomedin potencies of sera were assayed by following sulfation of mucopolysaccharides in chick embryo sterna in vitro. Apparent potencies of sera from hypophysectomized rats, maintained on a low-iodine diet, were restored to levels above normal by addition to the incubation medium of L-triiodothyronine at 10-7 mol/liter of serum. The potencies of normal rat, human, and fetal calf sera were raised 1.3-to 3-fold by addition of triiodothyronine at 10-9-10-7 mol/liter of serum. L-Thyroxine was about 10 times less effective than triiodothyronine. Triiodothyronine alone did not stimulate sulfation to nearly the same extent as triiodothyronine plus serum, even at higher concentrations. Serum could not be substituted in this system by any of six purified hormones, nor by trace metals or amino acids not included in the incubation mixture. It is concluded that triiodothyronine, in combination with a factor in serum, causes a rapid stimulation of sulfation in chick embryo cartilage, and that thyroid hormones may be involved in the action of normal serum on this tissue.Incorporation of sulfate into mucopolysaccharides of cartilage is stimulated by one or more factors in serum (1). These factors, which have been named somatomedins (2), are thought to be produced peripherally in response to growth hormone (1, 3). Part of the evidence for the involvement of growth hormone is the markedly lower stimulation of sulfation by serum from hypophysectomized rats (1,3,4) or hypopituitary humans (5-9) as compared to serum from normal individuals. Administration of purified growth hormone increased the titers of somatomedin in serum from hypopituitary rats (1, 3) or humans (6,7,9).We report here that in one system that has been used for assaying somatomedin, namely, cartilage from 12-day chick embryos (8, 10), somatomedin titers of serum from hypophysectomized rats were restored to values within or exceeding the normal range by addition in vitro of -3,5,3'-triiodothyronine (T3) at physiological concentrations. Addition of T3 to normal serum also increases its apparent somatomedin content. MATERIALS AND METHODST3 and L-thyroxine (T4) (Calbiochem) were dissolved in alkali and diluted rapidly in incubation medium before use. Bovine growth hormone was prepared according to Ellis (11) and Abbreviations: T3, I-3,5,3'-triiodothyronine; T4, L-thyroxine; NSILA, acid-soluble nonsuppressible insulin-like activity from serum.* To whom reprint requests should be addressed.purified by isoelectric focussing in a pH 7-9 gradient (12). Acid-soluble nonsuppressible insulin-like activity (NSILA), purified approximately 2000-fold from serum by acid ethanol extraction and chromatography on Sephadex G-75 (13), was a gift of Dr. E. R. Froesch. Purified relaxin (14) was provided by Dr. C. Schwabe.Hypophysectomized rats from which serum was obtained were operated on as weanlings and maintained for 6-8 weeks on a low-iodine diet, with or without daily maintenance doses of thyroid hormones, according to the protocol described by Denckla (15). In some gr...

Sulfate Uptake and Somatomedin Levels in the 'Little' (lit/lit) Mouse

“…Since hypophysectomized rats and Snell dwarf mice are deficient in pituitary hormones, some of which appear necessary, at least in chick cartilage (Audhya and Gibson 1975), for full expression of somatomedin activity, the interpretation of data concerned with factors controlling growth of these animals may be equivocal.…”

Triiodothyronine stimulates maturation of porcine growth-plate cartilage in vitro.

“…Thyroid hormones have been reported to have no effect on mammalian cartilage in vitro (9). In contrast, several in vitro studies show that thyroid hormones stimulate proteoglycan synthesis and potentiate somatomedin action in embryonic chick cartilage (7,8).…”

“…Changes in thyroid function in vivo lead to alterations in the secretion of many other hormones and some investigators have proposed that those alterations are responsible for the changes in osseous development (5,6). Although thyroid hormones have been shown to stimulate proteoglycan synthesis in vitro, in embryonic chick cartilage (7,8), no in vitro effects of thyroid hormones on mammalian cartilage have been demonstrated (9).…”

Growth Hormone Secretion and Plasma Somatomedin‐c in Primary Hypothyroidism

“…This could result from either relative resistance of Sm producing tissues to the action of GH or from direct inhibition of Sm synthesis or secretion. Alternatively, hypothyroid-induced growth failure may be independent of the GH-Sm axis since in uitro studies have shown that thyroid hormone stimulates indices of growth in cartilage explants (Audhya & Gibson, 1975;Froesch et al, 1976;Burch & Lebovitz, 1982). To further clarify these potential mechanisms we studied the regulation of one of the Sm, somatomedin-C (Sm-C), in patients with primary hypothyroidism by measuring G H responses to provocative stimuli, plasma concentrations of immunoreactive Sm-C before and during thyroid hormone therapy, and the plasma Sm-C responses following exogenous GH administration.…”