3,5-Di-iodo- l -thyronine suppresses TSH in rats in vivo and in rat pituitary fragments in vitro
Abstract
3,5-Di-iodo-l-thyronine (T2) is a naturally occurring metabolite of thyroxine (T4). Contrary to earlier findings, T2 has recently been shown to have rapid effects in rat liver and in mononuclear blood cells. In the experiments described here, T2 was tested to determine whether it has a TSH suppressive effect in rats in vivo and in rat pituitary fragments in vitro. In experiments over 2 weeks in rats in vivo, low doses of T2 (20–200 μg/100 g body weight per day) had no significant influence on body and organ weights, but significantly decreased TSH and T4 serum concentrations. At 200 μg/100 g per day, T2 suppressed TSH to 43% and T4 to 29% of control levels. At 1–15 μg/100 g per day, 3,5,3′-tri-iodo-l-thyronine (T3), used as a comparison to T2, had significant effects on TSH and T4 levels, and also on body weight. Fifteen μg T3/100 g per day decreased TSH to 44%, T4 to 25%, and body weight to 59% of control levels. In experiments over 3 months in rats in vivo, a low dose (25 μg/100 g per day) of T2 suppressed TSH to 60% and T4 to 57% of control levels and had no significant influence on other parameters. Conversely, 0·1 μg/100 g per day T3 had significant effects on body and organ weights as well as pellet intake, but a less pronounced TSH suppressive effect: TSH concentrations were unchanged and T4 concentrations were down to 80% of control values. In rat pituitary fragments in vitro, a clear suppression of TSH secretion after a TRH pulse was demonstrated. To summarise, T2 is a specific agonist in the negative feedback mechanism on TSH secretion at the pituitary level without other apparent thyromimetic effects. Journal of Endocrinology (1995) 145, 291–297
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3,5-T2, unlike its structural isomers 3,3′-T2 and 3′,5′-T2, is an active ligand for classical T3 receptors, binds with relatively high affinity, and modulates transcriptional activity of TR.
“3,5-T2, in contrast to its structural isomers 3,3′-T2 and 3′,5′-T2, is an active ligand for the classical T3 receptors (TR), where it binds with relative high affinity (Table 4) and modulates transcriptional activity of TR”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [85]
3,5-T2 treatment reduces serum TSH and T4 levels and TSH secretion from rat pituitary fragments.
“Horst et al. (1995) have shown that 3,5-T2 treatment reduced serum thyroid-stimulating hormone (TSH) and thyroxine (T4) levels as well as TSH secretion from rat pituitary fragments”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. 1995
The chronic effects of 3,5-T2 on proteins involved in thyroid hormone biosynthesis and thyroid hormone metabolism had not been assessed before this study.
“Despite the possible interference of 3,5-T2 on thyroid function (Horst et al. 1995, Baur et al. 1997, Moreno et al. 1998, García-G et al. 2007), to our knowledge, the chronic effects of 3,5-T2 on proteins involved in thyroid hormone biosynthesis (Kopp 2013) and thyroid hormone metabolism have not been assessed thus far.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. 1995
3,5-T2 by itself might exert negative feedback on TSH.
“demonstrating that 3,5-T2 by itself might be exerting the negative feedback, as suggested previously (Horst et al. 1995, Moreno et al. 1998).”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. 1995
Horst et al. (1995) found a reduction in serum T4 levels after 90 days of treatment with 25 μg of 3,5-T2/100 g BW.
“These authors also found a reduction in serum T4 levels after 90 days of treatment with 25 μg of 3,5-T2/100 g BW, which is in accordance with the results obtained herein.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. (1995)
Horst et al. (1995) did not observe any changes in body mass gain in rats treated for 3 months with the same dose of 3,5-T2.
“Horst et al. (1995) did not observe any changes in body mass gain in rats treated for 3 months with the same dose of 3,5-T2.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. (1995)
3,5-T2 reduces TSH secretion by rat pituitary fragments stimulated by TRH.
“Horst et al. (1995) showed that 3,5-T2 reduces TSH secretion by rat pituitary fragments stimulated by TRH.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Horst et al. (1995)
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Moreno, M., de Lange, P., Lombardi, A., Silvestri, E., Lanni, A., & Goglia, F. (2008) · Thyroid · doi:10.1089/thy.2007.0248 · Cited by 226 · see citing works
Padron, A. S., Neto, R. A. L., Pantaleão, T. U., de Souza dos Santos, M. C., Araujo, R. L., de Andrade, B. M., da Silva Leandro, M., de Castro, J. P. S. W., Ferreira, A. C. F., & de Carvalho, D. P. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0502 · Cited by 69 · see citing works
Köhrle, J., Lehmphul, I., Pietzner, M., Renko, K., Rijntjes, E., Richards, K., Anselmo, J., Danielsen, M., & Jonklaas, J. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00787 · Cited by 23 · see citing works
- Authors
- Horst, C., Harneit, A., Seitz, H. J., & Rokos, H.
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 1995-05-01
- Volume
- 145
- Issue
- 2
- Pages
- 291-297
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2065515775
- Cited by
- 28
- References
- 0
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 3 · 2014: 3 · 2013: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Keywords
- 3,5-diiodo-L-thyronine, T2*, triiodothyronine, thyroid-stimulating hormone, TSH suppression, thyroxine, thyroid hormone metabolism, body weight, dose-response relationship
- MeSH terms
- Animals, Depression, Chemical, Diiodothyronines, Dose-Response Relationship, Drug, Feedback, Male, Pituitary Gland, Thyrotropin, Thyroxine, Rats, Wistar, Culture Techniques, Rats
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