Abstract

The retinoid X receptor (RXR) agonist bexarotene can cause clinically significant hypothyroidism in cutaneous T cell lymphoma patients. The mechanism by which the RXR agonist produces this effect is unclear. We have studied the impact of a selective RXR agonist (rexinoid), LG100268, on rat thyroid axis hormones and show that the acute phase of hypothyroidism is associated with reduced pituitary TSH secretion. A single oral administration of LG100268 to naive Sprague Dawley rats causes a rapid and statistically significant decline in TSH levels (apparent in 0.5–1 h). Total T4 and T3 levels decline more gradually, reaching statistical significance 24 h after treatment. Increasing doses of LG100268 produce greater suppression of thyroid axis hormones. To investigate the mechanism(s) mediating this suppression, we determined pituitary TSHβ mRNA, TSH protein levels, and TRH-stimulated TSH secretion. Two hours after treatment, neither TSHβ mRNA nor TSH protein levels were altered by LG100268. However, LG100268 treatment reduced the area under the curve for TRH-stimulated TSH secretion by 54%. We have identified an unexpected mechanism by which rexinoids induce hypothyroidism by acutely reducing TSH secretion from the anterior pituitary. This mechanism is independent of the rexinoid’s previously demonstrated inhibition of TSHβ gene transcription.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.