Recombinant human thyrotropin stimulates thyroid angiogenesis in vivo.
BACKGROUND
Endogenous TSH and rhTSH stimulate thyroid growth by a direct effect on thyrocytes. Our hypothesis was that rhTSH may also stimulate thyroid angiogenesis.


METHODS
A normal human thyroid tissue sample was grafted into the epigastric area of 14 nude mice. Mice were divided in two groups of 7. The first group (treated mice) received rhTSH stimulation (0.014 UI/mouse/day for 3 weeks), while the second group (control mice) had saline. Histological study with special focus on vascular characteristics was performed by image analysis at day 21 for each graft. VEGF immunostaining score, determined by immunohistochemistry, was defined as the percentage of labeled thyrocytes score, plus an intensity score.


RESULTS
Thyroid follicles showed signs of increased colloid re-uptake activity in rhTSH group within a larger surface area than controls (p <0.01). Thyrocytes were taller in the rhTSH group (p <0.01). The diameter of capillary vessels was larger and the microvessels expansion more important in the rhTSH group (p <0.02). Relative capillary area, defined as the ratio between capillary area and follicular area, was also higher in the rhTSH group (p <0.02). VEGF immunostaining score was increased in the rhTSH group (p <0.01).


CONCLUSIONS
rhTSH stimulates angiogenesis and local VEGF expression in normal human thyroid.
Klein
Marc
M
Department of Endocrinology, University Hospital of Nancy, Nancy, France. m.klein@chu-nancy.fr
Brunaud
Laurent
L
Muresan
Mihaela
M
Barbé
Françoise
F
Marie
Béatrice
B
Sapin
Remy
R
Vignaud
Jean-Michel
JM
Chatelin
Jérôme
J
Angioï-Duprez
Karine
K
Zarnegar
Rasa
R
Weryha
Georges
G
Duprez
Adrien
A
D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000494:pharmacology*; D013961:Thyroid Gland / Q000098:blood supply* / Q000502:physiology*; D013972:Thyrotropin / Q000737:chemistry*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D013972:Thyrotropin