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09-03-2006 | Thyroid | Article

Influence of rexinoids on HPT-axis delineated

Abstract

Free abstract

A team of French and US researchers has found that retinoid X receptor (RXR)-selective retinoids (rexinoids) have multiple effects on the hypothalamic-pituitary-thyroid (HPT) axis.

"An understanding of this mechanism will provide insights into the role of retinoids and receptors in thyrotrope function and may be useful as therapy in patients with disorders of TSH regulation including TSH-secreting adenomas and the syndrome of thyroid hormone resistance," the scientists state in the journal Endocrinology.

The effects of vitamin A (retinol) on thyroid hormone production and action have been known since the 1940s, when patients with hyperthyroidism were treated with the vitamin. Retinol is thought to suppress thyroid hormones through its effects on retinoid receptors.

Recent research findings that indicated synthetic rexinoids can bring about central hypothyroidism in humans.

For the current study, Vibha Sharma, from the University of Colorado Health Sciences Center, and team extended explorations into the role of rexinoids on the HPT axis in mice and TSH regulation in a thyrotrope-derived cell line.

They found that the synthetic rexinoid LG 268 suppressed thyroid stimulating hormone (TSH) and T4 levels in the mice.

Conversely, levels of hypothalamic thyrotropin-releasing hormone (TRH) messenger (m)RNA was unaffected by the administration of rexinoids.

However, steady-state pituitary TSH β mRNA levels were significantly lowered because of the rexinoid treatment, "suggesting a direct effect of rexinoids on thyrotropes," the researchers say.

Type 2 iodothyronine deiodinase (D2) mRNA levels and activity were also suppressed by the synthetic rexinoid in thyrotrope-derived cells.

"RXR-selective rexinoids have multiple effects on the HPT axis," Sharma et al summarize.

"Rexinoids directly suppress TSH secretion, TSH β mRNA levels and promoter activity, and D2 mRNA levels but have no direct effect on hypothalamic TRH levels."