The effect of hypoglycemia on hypothalamic thyrotropin-releasing hormone (HRH) in the rat.

A rapid radioimmunoassay for TRH with a high degree of specificity and sensitivity is described. The procedure is capable of measuring TRH in amounts less than 15 pg/tube. Such an assay system has enabled us to study the effect of hypoglycemia on hypothalamic TRH content. Forty-eight female, adult Holtzman rats were divided into 8 groups of 6. Regular insulin was injected intraperitoneally into each rat except for the basal group. A separate batch of similar rats was studied in the same fashion except that saline was injected instead of insulin. Each group of rats was decapitated and the trunk blood collected at 0, 15, 30, 45, 60, 90, 120 and 180 min post-injection. Appropriate tissues were rapidly taken and immediately extracted in ice-cold methanol. Hypothalamic TRH, pituitary TSH, serum TSH and serum triiodothyronine (T3) and thyroxine (T4) were serially determined. In the insulin-treated group, a rapid fall in blood sugar was observed reaching a nadir in 15 min. Hypothalamic TRH fell from a basal mean +/- SE value of 3.25 +/- 0.31 ng to 1.54 +/- 0.14 ng/hypothalamus (P less than 0.01). Pituitary TSH decreased from 10.0 +/- 0.9 mug to a low of 2.6 +/- 0,8 mug/pituitary (P less than 0.02) at 30 min postinsulin. Serum TSH increased from a basal level of 42.5 +/- 20.5 muU/mo to a peak of 102.1 +/- 10.0 muU/ml 45 min (P less than 0.05) after insulin administration. The incremental change in serum T3 occurred at 90 min when T3 levels increased from a baseline of 107.5 +/- 53.7 ng/100 ml to a peak of 711.7 +/- 20.2 ng/100 ml (P less than 0.01). No changes in T4 were observed. The control group of rats did not show significant changes in hypothalamic TRH. The results of the study indicate that hypoglycemia can induce depletion (presumably release) of hypothalamic TRH with a consequent cascade stimulation of the pituitary-thyroid axis.