Thyroid vascular conductance: Differential effects of elevated plasma thyrotropin (TSH) induced by treatment with thioamides or TSH-releasing hormone

Abstract

We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250-280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3-0.9 μg T4 plus 0.075-0.225 μg T3/100 g·day via continuous sc infusion), or 4) TRH (9-1200 μg TRH/100 g·day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney and pancreas were determined using the reference sample version of the radioactive microsphere technique. PTU treatment led to the expected hypothyroidism, increased plasma TSH concentrations (959 ± 66 vs. 154 ± 22 ng/dl), increased thyroid weight (9.19 ± 0.36 vs. 4.60 ± 0.15 mg/100 g), and increased thyroid vascular C/mass (495 ± 51 vs. 127 ± 20 μl/mm Hg·g/ min). PTU-treated rats receiving partial thyroid hormone replacement demonstrated a dose-related suppression of plasma TSH, thyroid weight, and thyroid vascular C. Although, TRH treatments resulted in increased plasma TSH concentrations (e.g. 1200 μg TRH, 706 ± 46 ng/dl) and thyroid weight (e.g. 1200 μg TRH, 7.45 ± 0.41 mg/100 g), thyroid vascular C per tissue mass was not significantly increased after any TRH treatment (e.g. 1200 μg TRH, 166 ± 19 μl/mm Hg·g/min). Thus, at similarly elevated plasma TSH concentrations, the thyroid vascular C/mass of PTU- and TRH-treated rats constituted separate populations. Both PTU- and TRH-induced thyroid growth were accompanied by similar alterations in thyroid gland morphology (i.e. increased cellular mass with little change in the total amount of colloid). To investigate the mechanisms involved, groups of rats were treated for 6 days as follows: 1) control, 2) PTU or methimazole (25 mg MMI/day, ip), 3) PTU or MMI plus thyroid hormone replacement (1.2 μg T4 plus 0.3 μg T3/d·100 g), 4) TRH (12 μg/100 g·day), and 5) PTU or MMI, thyroid hormones, and TRH. PTU or MMI treatment in the absence of elevations of plasma TSH (i.e. thyroid hormone replaced) had no effect on thyroid vascular C/mass, nor did TRH treatment, which elevated plasma TSH alone. However, in all groups in which plasma TSH was elevated in the presence of PTU or MMI (i.e. groups 2 and 3 above), thyroid vascular C/ mass was significantly increased. We conclude that thioamide treatment (PTU or MMI) alters the sensitivity of the thyroid gland to the effects of elevated plasma TSH on thyroid vascular C.