Megalin facilitates thyroid hormone secretion
by removing thyroid hormone–poor thyroglobulin
(March 2004)
The background of the study.
Thyroglobulin, located in the lumen of thyroid follicles, is the
site of both synthesis and storage of thyroxine (T4) and triiodothyronine
(T3). It enters thyroid cells from the lumen in two ways. One is
by the formation of droplets that are taken into thyroid cells and
then broken down to release T4 and T3. The other is by binding to
megalin, a protein located in the membrane of the cells. The megalin–thyroglobulin
complex is carried across the cell to the basal membrane, where
the thyroglobulin is released. This study determined whether the
hormonal content of thyroglobulin affects its uptake by megalin.
How the study was done and the
results. More rat thyroglobulin
(Tg) containing no T4 and T3 (hormone-poor Tg) was taken up by and
passed through rat thyroid cells grown on a filter to a lower chamber
than was Tg containing T4 and T3 (hormone-rich Tg), and the increase
was blocked when anti-megalin antibodies were added. Addition of
hormone-rich Tg to the cells resulted in the appearance of some
T3 in the lower chamber, indicative of breakdown of Tg. Concurrent
addition of anti-megalin antibodies increased the content of T3
in the lower chamber, indicating more breakdown of hormone-rich
Tg despite the inhibition of megalin-mediated uptake of Tg.
In rats given a drug to inhibit T4 and T3 synthesis and T4 to prevent
hypothyroidism, the thyroidal content and distribution of megalin,
as determined by immunofluorescence, was similar to that in control
rats. Serum Tg concentrations were higher in the treated rats. Anti-Tg
antibodies precipitated serum Tg in both groups, but anti-megalin
antibodies precipitated serum Tg only in the treated rats, presumably
because some of the Tg in the circulation in these rats was megalin-bound.
The conclusions of the study.
The megalin pathway of thyroglobulin metabolism in the thyroid gland
serves to remove hormone-poor thyroglobulin from the gland, and
therefore increase breakdown of hormone-rich thyroglobulin.
The original article.
Lisi S, Pinchera A, McCluskey RT, Willnow TE, Refetoff S, Marcocci
C, Vitti P, Menconi F, Grasso L, Luchetti F, Collins AB, Marino
M. Preferential megalin-mediated transcytosis of low-hormonogenic
thyroglobulin: a control mechanism for thyroid hormone release.
Proc Natl Acad Sci USA 2003;100:14858-63.
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