Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase
Open accessAbstract
Suppression of TSH release from the hypothyroid thyrotrophs is one of the most rapid effects of 3,3′,5′-triiodothyronine (T 3 ) or thyroxine (T 4 ). It is initiated within an hour, precedes the decrease in TSH β mRNA inhibition and is blocked by inhibitors of mRNA or protein synthesis. TSH elevation in primary hypothyroidism requires both the loss of feedback inhibition by thyroid hormone in the thyrotrophs and the positive effects of TRH. Another event in this feedback regulation may be the thyroid hormone-mediated induction of the TRH-inactivating pyroglutamyl peptidase II (PPII) in the hypothalamic tanycytes. This study compared the chronology of the acute effects of T 3 or T 4 on TSH suppression, TRH mRNA in the hypothalamic paraventricular nucleus (PVN), and the induction of tanycyte PPII. In wild-type mice, T 3 or T 4 caused a 50% decrease in serum TSH in hypothyroid mice by 5 h. There was no change in TRH mRNA in PVN over this interval, but there was a significant increase in PPII mRNA in the tanycytes. In mice with genetic inactivation of the type 2 iodothyronine deiodinase, T 3 decreased serum TSH and increased PPII mRNA levels, while T 4 -treatment was ineffective. We conclude that the rapid suppression of TSH in the hypothyroid mouse by T 3 occurs prior to a decrease in TRH mRNA though TRH inactivation may be occurring in the median eminence through the rapid induction of tanycyte PPII. The effect of T 4 , but not T 3 , requires the type 2 iodothyronine deiodinase.
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T3 upregulates expression of pyroglutamyl peptidase II in tanycytes of the median eminence, which degrades locally released TRH.
“in the tanycytes located in the median eminence, T3 can upregulate the expression of pyroglutamyl peptidase II, which is a highly specific TRH peptidase that degrades the locally released TRH before it reaches the portal vein system (19).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [19]
The Results report a significant rise in PPII mRNA in median-eminence tanycytes after T3 treatment, and the Introduction identifies PPII as a highly specific TRH peptidase. The Discussion describes degradation of TRH at tanycyte processes in the median eminence as a potential mechanism, not a demonstrated event before TRH reaches the portal vein system. Our copy provides no direct evidence for that precise route or timing. (LLM, conf=0.86)
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Cites
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
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Self-citation
- Authors
- Marsili, A., Sanchez, E., Singru, P., Harney, J. W., Zavacki, A. M., Lechan, R. M., & Larsen, P. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Tufts Medical Center (US)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2011-07-25
- Volume
- 211
- Issue
- 1
- Pages
- 73-78
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- PMC
- PMC3558748
- OpenAlex
- W2121662324
- Cited by
- 27
- References
- 6
- Citations by year
- 2026: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 3 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK- 37021)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 37021, R01DK037021, DK36256, R56DK037021, R01DK036256, T32DK007529)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- thyroxine, triiodothyronine, type 2 deiodinase, TSH suppression, thyrotropin-releasing hormone, tanycytes, paraventricular nucleus, median eminence, hypothyroidism, hypothalamic-pituitary-thyroid axis
- MeSH terms
- Iodothyronine Deiodinase Type II, Aminopeptidases, Animals, Disease Models, Animal, Hypothyroidism, Injections, Intraperitoneal, Iodide Peroxidase, Mice, Inbred C57BL, Paraventricular Hypothalamic Nucleus, Pyrrolidonecarboxylic Acid, RNA, Messenger, Antithyroid Agents, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Triiodothyronine, Mice, Knockout, Mice
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