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Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas

Le Dafniet M, Brandi A-M, Kujas M, Chanson P, Peillon F. Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas. Eur J Endocrinol 1994:130:559–64. ISSN 0804–4643

In order to see whether, in thyrotropic adenomas with thyrotoxicosis, plasma thyroid hormones regulate the thyrotropin-releasing hormone (TRH) binding sites and the thyrotropin (TSH) response to TRH, we investigated: the presence of TRH binding sites in two cases of thyrotropic adenomas associated with hyperthyroidism and in one case of thyrotropic adenoma secondary to thyroid failure; and the in vitro effect, in a perifusion system, of triiodothyronine (T₃) on the response of TSH to TRH in three cases of TSH-secreting adenomas associated with hyperthyroidism. The TRH binding sites were absent in the adenomas associated with high levels of circulating thyroid hormones, whereas they were present in the adenoma secondary to primary thyroid failure (K₄ =47 nmol/l, B_max = 40 nmol/ kg membrane proteins). In vitro, the three adenomas spontaneously released TSH in the perifusion medium (1.49 ±0.06 (mean ± SEM), 7.25±0.12 and 16.73±0.36 mIU·^–1·10⁶ cells^–1·2 min^–1) and exhibited an ample TSH response to 10^–7 mol/l TRH pulses. In two cases, tumoral secretion of fragments was compared with those of fragments maintained since the time of surgical removal in the presence of 10^–8 mol/l T₃. The TSH responses to TRH were abolished in the presence of T₃ in these two cases. We conclude that thyrotropic adenomas associated with hyperthyroidism are still controlled in vivo by T₃. In particular, T₃ regulates the TSH response to TRH, probably via a down-regulation of the TRH binding sites.

Michèle Le Dafniet, Unité INSERM 223, Faculté de Médecine, Pitié-Salpêtrière, 105 Boulevard de l'Hôpital, 75013 Paris, France

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