An Elevation of Plasma TSH Concentration in Spontaneously Hypertensive Rats (SHR)

Abstract

Thyroidal radioiodine uptake and release varied somewhat from strain to strain in rats, but no abnormal elevation or depression has been reported in rats (1). Okamoto (2) isolated a new strain from Wistar rats with spontaneous hypertension and noticed that this strain of rats had bigger thyroids, adrenals, and pituitaries than those of the control strain. Since coincidence of an increase of pituitary and thyroid weights suggests an increased production and release of TSH by the anterior pituitary, the present experiment was undertaken to study TSH concentrations of the anterior pituitary and circulating blood and to measure thyroid activity in response to an increase of blood TSH. The data indicated that spontaneously hypertensive rats (SHR) had not only high blood pressure but also an abnormal increase of blood TSH.Materials and Methods. Control rats and SHR were obtained from two different sources. One substrain of SHR was obtained from NN Laboratory, and the other substrain of SHR was bred in Kyoto University. Only male rats were used for the experiments. The animals were fed laboratory chow and water ad lib. unless otherwise stated. In experiment 2, animals were fed low-iodine diets beginning 10 days before radioiodine injection. Radioiodine (1.7 pCi of l 3 I I ) was injected intraperitoneally, and autopsy was performed 24 hr later. At autopsy, blood was obtained by cardiac puncture, using heparinized syringes. Plasmas were separated and kept at -20" until use. The pituitary, thyroid, and adrenal were cleanly dissected out and weighed on a torsion balance. Thyroid and adrenal weights were expressed as mg/100 g body wt. In experiment 3, 2 pg T4 was injected intraperitoneally daily for 7 days beginning 3 days after thyroidectomy. Bloods were drawn 24 hr after the last dose of T4. Pituitary and plasma TSH concentrations were measured as reported previously (3). Plasma thyroxine (T4) concentration was measured by competitive binding assay. Plasma triiodothyronine (T3) concentration was measured by radioimmunoassay. To rule out the error associated with measurements of T4, T3 and TSH, pooled plasma was always used as the standard. Plasma PB1311 was measured as reported previously (4). Blood pressures were measured by tail-pulse pickup in unanesthetized rats. The data were analyzed for statistical significance by the Student t test.Results. Experiment I . Serum thyroxine, triiodothyronine, and TSH levels, and pituitary contents of TSH. In the first step of this experiment, rats were obtained from NN Laboratory Blood pressure of SHR was 185 =t 7 mm Hg (mean =t SE), while it was 135 =t 6 mm Hg (mean =t SE) in the controls. Plasma T4 was slightly but significantly less in SHR than in the controls. Plasma T3 concentration was the same in both SHR and control groups (Table I). However, plasma TSH concentration was significantly elevated in SHR. Also, pituitary content of TSH increased significantly in SHR.In the second part of this experiment, rats were obtained from Kyoto University. Blood pressure of SHR was 194 =t 7 ...

Antisense Inhibition of Thyrotropin-Releasing Hormone Reduces Arterial Blood Pressure in Spontaneously Hypertensive Rats

“…SHR are characterized by several neuroendocrine abnormalities, including a chronic hypersecretion of TSH of unknown etiology associated with normal plasma T3 and T4 levels. 23 This inappropriately high TSH secretion in euthyroid SHR may be the result of an impaired hormone negative feedback regulation of the central TRH system or a inappropriate pituitary TSH production. 24 Accordingly to other authors and our own previous data, we showed that SHR in basal conditions present a higher (3-fold) plasma TSH concentration compared with control WKY rats.…”

Vascular and renal function in experimental thyroid disorders

“…Several variables were studied to determine if thyroid weight increases were secondary to hyperor hypofunction of the gland, with T 3 and T 4 serum levels being the most frequently measured. In spontaneously hypertensive rats, age-dependent variations (170) have been seen and contradictory results in adult rats have been reported (167,170,171). A decrease in T 3 and T 4 serum levels in Dahl rats (172) and a reduction in T 3 serum concentrations in encapsulated hypertensive rats (169) were observed.…”

“…In spontaneously hypertensive rats (167), mineralocorticoid (168) and renal encapsulated hypertensive rats (169), an increase in thyroid gland weight has been reported. A sigmoid relationship was observed between the ratio of thyroid weight to body weight and systolic blood pressure.…”

Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat.

“…These include lowered levels of plasma thyroxine and triiodothyronine, elevated plasma thyroid-stimulating hormone, consequent increased thyroid weight and radioiodine uptake, 50 and impairment of synthesis or secretion of thyroid hormones in response to thyroid-stimulating hormone. 51 It is also noteworthy that Takeichi et al 19 proposed that the natural thymocytotoxic autoantibody they observed in many SHR is an IgM molecule, as indicated by its elution pattern on gel filtration and sensitivity to reduction by 2-mercaptoethanol.…”