ABSTRACT

SR-202 is a non-iodinated potential lipid-altering agent. When administered (100 mg) three times per day for 3 days to six euthyroid subjects it was associated with a 30 ± 3% (mean ± s.e.m.) fall in 3,3′,5-tri-iodothyronine(T₃)(P < 0·001), a reciprocal 104 ± 14% rise in 3,3′,5′-tri-iodothyronine (reverse T₃, rT₃) (P < 0·01), and a 37 ± 7% rise in thyroxine (T₄) (P < 0·001). Basal and TRH-stimulated TSH did not change. These results suggested that SR-202 was acting as an inhibitor of the peripheral monodeiodination of T₄ to T₃.

During a second study the same subjects received the same dose of SR-202 for a further 3 days following 15 days of progressive substitutive treatment with l-T₄, which they continued to take at 200 μg/day until the end of the study. Despite higher levels of thyroid hormones in the substituted subjects, similar results were observed, serum T₃ falling by 40 ± 2% (P < 0·001), serum rT₃ and T₄ rising by 168 ± 24% (P < 0·01) and 37 ± 9% (P < 0·01) respectively. These changes provide compelling evidence that SR-202 is an inhibitor of the peripheral conversion of T₄ to T₃ that acts on thyroid hormone metabolism without provoking a counter-regulatory pituitary response. It might prove to be a useful tool for the clinical investigation of thyroid function.

J. Endocr. (1987) 112, 171–175

SUMMARY

The binding of ¹²⁵I-labelled human growth hormone (HGH) to the 'lactogenic' binding sites of rat liver membranes has been shown to be highly dependent on the oestrogen and androgen status of the animal from which the membranes were prepared. Oestradiol treatment of either male or female rats induced a highly significant rise in HGH binding. The minimum effective dose used was 2–5 μg/day and the rise in HGH binding was apparent after 4 days of treatment. Following cessation of oestradiol treatment of male rats HGH binding declined with a half-time of approximately 9 days. In contrast to the stimulatory effect of oestrogen, treatment of female rats with testosterone propionate (minimum effective dose 100–200 μg/day) led to a marked reduction in HGH binding. The influence of both oestrogens and androgens was confirmed following the removal of endogenous sex steroids by adrenalectomy–ovariectomy of female rats and castration of male rats. Scatchard analysis showed that, with the possible exception of adrenalectomy–ovariectomy, all pharmacologically and physiologically induced changes in HGH specific binding reflected changes in binding site capacity; there were no changes in binding affinity. While earlier studies have indicated that the oestrogen effect is primarily indirect and is mediated by the pituitary gland, the mode of action of the androgens is currently unknown. The relatively slow response of HGH binding to hormonal changes would support an indirect action for both the sex steroids. The stimulatory effect of oestrogens and the inhibitory effect of androgens may provide an explanation for the marked sex difference in HGH binding to rat liver membranes.

Abstract

Interleukin-1β has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1β dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1β. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1β-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1β-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor N ^G-monomethylarginine did not ameliorate the effect of interleukin-1β on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1β for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1β-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1β in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells.

Journal of Endocrinology (1996) 151, 147–157