Hypothyroidism induces expression of the peptide transporter PEPT2.

Abstract

The kidney is a target organ for thyroid hormone action and a variety of renal transport processes are altered in response to impaired thyroid functions. To investigate the effect of thyroid hormone on the expression of the renal proximal tubular high-affinity-type H(+)-peptide cotransporter (PEPT2) in rats, hypothyroidism was induced in animals by administration of methimazole (0.05%) via drinking water. After 7 weeks of treatment, hypothyroidism was confirmed by determining serum free T(3) and free T(4) concentrations. Northern blotting was used to examine the expression of PEPT2 mRNA in kidney tissues from hypothyroid rats compared to control rats. Hypothyroidism resulted in an increased level of total renal PEPT2 mRNA (121.1+/-3.3% vs. control 100+/-2.8%; p=0.008). The mRNA results were confirmed by immuno-blotting, which demonstrated significantly increased protein levels (162% vs. control 100%; p<0.01). Immunohistochemistry also revealed increased PEPT2 protein levels in the proximal tubules of treated compared to non-treated rats. In summary, PEPT2 is the first proximal tubule transporter protein that shows increased expression in states of hypothyreosis. As PEPT2 reabsorbs filtered di- and tripeptides and peptide-like drugs, the present findings may have important implications in nutritional amino acid homeostasis and for drug dynamics in states of altered thyroid function.

• Authors: Frank Döring, Roland Schmitt, Wanja M Bernhardt, Maja Klapper, Sebastian Bachmann, Hannelore Daniel, David A Groneberg
• Journal: Biological chemistry (Biol Chem) Vol. 386 Issue 8 Pg. 785-90 (Aug 2005) ISSN: 1431-6730 [Print] Germany
• PMID: 16201874 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antithyroid Agents
• Peptides
• RNA, Messenger
• Symporters
• hydrogen-coupled oligopeptide transporter PepT2
• Methimazole

Topics

• Animals
• Antithyroid Agents (pharmacology)
• Biological Transport
• Blotting, Northern
• Gene Expression
• Hypothyroidism (blood, chemically induced, metabolism)
• Immunohistochemistry
• Kidney Tubules, Proximal (drug effects, metabolism)
• Methimazole
• Peptides (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Symporters (genetics, metabolism)