PITUITARY–THYROID FUNCTION IN THE RHESUS MONKEY (MACACA MULATTA)

Abstract

The mean concentration of thyroxine (T4) in the plasma of the rhesus monkey Macaca mulatta (53 ± 8 (s.d.) nmol/l) is less than the lower limit of the range of concentrations normally found in man; conversely, the mean concentration of tri-iodothyronine (T3) in monkey plasma (2·45 ± 0·52 (s.d.) nmol/l) is at the upper end of the normal human range. The basal concentrations of TSH in the plasma, as measured by radioimmunoassay, were comparable in the two species (mean concentration of TSH in monkey plasma 1·53 mu./l; range 0·2–2·6 mu./l). The administration of radioactive iodine (13–15 mCi Na131I) to these monkeys regularly induced hypothyroidism. The concentration of TSH in the plasma began to rise 3 weeks after the administration of radioactive iodine and reached a maximum and sustained level (30–300 mu./l) after 3 months, at which time the concentrations of T4 and T3 in the plasma were immeasurable. Other pituitary and adrenal functions were unaffected by the hypothyroid state. Protracted sedation of normal monkeys with phencyclidine hydrochloride resulted firstly within hours in a decline in the concentration of T3 in the plasma without any corresponding alteration in the concentration of T4 and secondly, after 24 h, in a marked rise in the concentrations of both T4 and TSH. The connection between these changes is not clear but phencyclidine does not seem to be a suitable sedative for prolonged studies of the pituitary– thyroid system in normal monkeys. In contrast, sedation with phencyclidine did not affect the concentration of TSH in the plasma of hypothyroid monkeys provided that their body temperature was maintained near normal; the level of TSH fell if the monkey became cold when sedated and rose if it became overheated. The rise in the level of TSH in the plasma of normal monkeys after administration of synthetic thyrotrophin releasing hormone (TRH) was less than that observed in man, although the effect of the increase upon the plasma T3 concentration was similar in the two species. The response of monkeys to incremental doses of TRH showed that a maximum response was obtained at a lower equivalent dose (1·0 μg/kg body weight) than in man, but administration of this dose (or a greater one) to hypothyroid monkeys caused only small increases in the concentration of TSH in the plasma. The rapid intravenous injection of 0·2 or 2·0 μg T3 had no effect on the level of TSH in the plasma of hypothyroid monkeys, but 20 μg caused a progressive decline which reached a nadir 35% below the baseline at 5 h; the level of TSH returned to its basal value after 24 h. The raised concentration of TSH in the plasma of hypothyroid monkeys could be reduced to the normal range by the repeated administration of 20 μg T3 over 3 or 4 days.