3,5-Diiodo-l-Thyronine Stimulates Type 1 5′Deiodinase Activity in Rat Anterior Pituitaries in Vivo and in Reaggregate Cultures and GH3 Cells in Vitro1
Abstract
Local deiodination of L-thyroxine (T4) to the active thyroid hormone T3 via two 5'deiodinase isoenzymes (5'DI and 5'DII) plays an important role for various T3-dependent functions of the anterior pituitary (AP). Recently, it was reported that 3,5-T2, the 5'deiodination product of T3, acts as a specific agonist in the feedback mechanism on TSH secretion at the pituitary level. We now examined the effects of 3,5-T2 on pituitary 5'deiodinase activities in vivo in male, adult rats and in vitro using rat AP reaggregate cultures and the somatomammotroph cell line GH3. 5'DI activity in the AP was transiently increased after a single injection of 3,5-T2. Serum TSH levels declined, and 24 h after 3,5-T2 application, betaTSH steady-state mRNA levels in the APs were markedly lower. In reaggregate cultures of the AP, 3,5-T2 stimulated 5'DI activity 24 h after application, dose-dependently. Compared with 5'DI activities, those of 5'DII were an order of magnitude lower, in vivo as well as in vitro, and were rapidly and transiently decreased by the higher dose of 3,5-T2. GH3 cells responded to 3,5-T2 and T3 by an 1.7-fold stimulation of 5'DI activity. Stimulation of DNA-binding was demonstrated in electrophoretic mobility shift assays for a specific RXR-containing protein complex with a DR+4 thyroid hormone response element of the human type 1 5'DI promoter using nuclear extracts from GH3 cells treated with 3,5-T2. In summary, 3,5-T2 and T3 exert direct thyromimetic effects on 5'DI activity…
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3,5-T2 stimulates growth hormone production and secretion in somatotrophs.
“In addition to its action on TSH suppression in thyrotropes, 3,5-T2 also stimulates growth hormone production and secretion in somatotrophs (86).”
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 [86]
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 [86]
3,5-T2 increases pituitary type 1 iodothyronine deiodinase (D1) activity and transiently decreases type 2 iodothyronine deiodinase (D2) activity in rats.
“Moreover, 3,5-T2 increases pituitary type 1 iodothyronine deiodinase (D1) activity and transiently decreases type 2 iodothyronine deiodinase (D2) activity in rats (Baur et al. 1997)”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Baur et al. 1997
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 Baur et al. 1997
3,5-T2 stimulates D1 activity in rat anterior pituitaries in vivo.
“In accordance with our data, Baur et al. (1997) showed that 3,5-T2 stimulates D1 activity in rat anterior pituitaries in vivo.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Baur et al. (1997)
A single dose of 3,5-T2 reduces serum Tsh and pituitary β-TSH (Tshb) mRNA levels.
“Moreover, a single dose of 3,5-T2 was shown to reduce serum Tsh and pituitary β-TSH (Tshb) mRNA levels (Baur et al. 1997).”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Baur et al. 1997
Cites
SILVA, J. E., DICK, T. E., & LARSEN, P. R. (1978) · Endocrinology · doi:10.1210/endo-103-4-1196 · Cited by 189 · see citing works
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Metabolic Effects of Thyroid Hormone Derivatives
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
Jonas, W., Lietzow, J., Wohlgemuth, F., Hoefig, C. S., Wiedmer, P., Schweizer, U., Köhrle, J., & Schürmann, A. (2015) · Endocrinology · doi:10.1210/en.2014-1604 · Cited by 90 · see citing works
Self-citationPadron, 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
Self-citation
- Authors
- Baur, A., Bauer, K., Jarry, H., & Köhrle, J.
- Affiliations
- University of Würzburg (DE)
- Max Planck Society (DE)
- Universitätsmedizin Göttingen (DE)
- ORCID
- Köhrle, J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1997-08
- Volume
- 138
- Issue
- 8
- Pages
- 3242-3248
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1999347033
- Cited by
- 42
- References
- 1
- Citations by year
- 2023: 1 · 2022: 1 · 2020: 3 · 2019: 2 · 2017: 2 · 2016: 2 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- 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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- 3,5-diiodo-L-thyronine, anterior pituitary, GH3 cells, serum TSH
- MeSH terms
- Analysis of Variance, Animals, Base Sequence, Cell Communication, Cell Line, Diiodothyronines, Dose-Response Relationship, Drug, Electrophoresis, Humans, Iodide Peroxidase, Isomerism, Male, Pituitary Gland, Anterior, RNA, Messenger, Thyronines, Thyrotropin, Time Factors, Blotting, Northern, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Rats
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