Evidence for co-ordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status of the thyroid follicles, and the microvascular bed during chronic stimulation by low iodine and propylthiouracyl in old mice.
Vasoactive and angiogenic factors are involved in the autocrine/paracrine thyroid regulation of microvascular bed during goiter development. In the thyroid of old mice, the presence of slowly functioning ('cold') follicles allowed us to study the microvascular regulation of each follicle in correlation with the immunohistochemical expression of vascular endothelial growth factor (VEGF) and nitric oxide synthase III (NOSIII). Mice aged 20 months did or did not receive a goitrogenic treatment (low iodine diet and propylthiouracyl), and their thyroids were processed for light and electron microscopy, and for autoradiography. The relative volumes (Vv) of the capillaries, the number of vessels per follicular area, the mean capillary area and the number of [(3)H]thymidine labeled nuclei were measured separately for 'hot' and 'cold' follicles. Already in control mice, the capillary bed surrounding 'hot' follicles was significantly larger than that seen around 'cold' follicles, because of larger diameters and twice the number of capillaries. This difference persisted whatever the length of the stimulatory treatment. During this treatment, the Vv of the capillaries increased to a larger extent around 'hot' follicles than around 'cold' ones. All vascular changes around 'cold' follicles were less extended and the increase in the capillary diameter was delayed. In control mice, the 'cold' follicles were negative for NOSIII and positive for VEGF while 'hot' follicles were positive for both. During stimulation, all follicles became progressively NOSIII positive. These data support the concept of 'angio-follicular units' in the thyroid and demonstrate their differential regulation in chronic stimulation during which local secretion of VEGF and NO is clearly involved.
Gérard
A C
AC
Histology Unit, Université Catholique de Louvain, Medical School, Brussels, Belgium.
Xhenseval
V
V
Colin
I M
IM
Many
M C
MC
Denef
J F
JF
D000375:Aging / Q000502:physiology; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D002196:Capillaries / Q000473:pathology; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism*; D007150:Immunohistochemistry; D007455:Iodine / Q000008:administration & dosage* / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D011441:Propylthiouracil / Q000494:pharmacology*; D012016:Reference Values; D013961:Thyroid Gland / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D013956:Antithyroid Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011441:Propylthiouracil; D007455:Iodine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse