Evidence for co-ordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status ofthe 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 t hyroid regulation of microvascular bed during goiter development. In the thyroid of old mice, the presence of slowly functioning ('cold') fol licles allowed us to study the microvascular regulation of each follicle in correlation with the immunohistochemical expression of vascular endothelia l 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 electro n microscopy, and for autoradiography. The relative volumes (Vv) of the cap illaries, the number of vessels per follicular area, the mean capillary are a and the number of [H-3]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 lar ger diameters and twice the number of capillaries. This difference persiste d whatever the length of the stimulatory treatment. During this treatment, the Vv of the capillaries increased to a larger extent around 'hot' follicl es than around 'cold' ones. All vascular changes around 'cold' follicles we re 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 a nd demonstrate their differential regulation in chronic stimulation during which local secretion of VEGF and NO is clearly involved.