Neuroendocrine effects of caffeine. II. Effects on thyrotropin and corticosterone secretion.

Caffeine injected i.p. to rats decreased serum thyrotropin and markedly increased serum corticosterone with ED50 values of 40 to 50 mg/kg. Adrenalectomy did not affect the response of thyrotropin to caffeine. Theophylline was as potent as caffeine in inhibiting thyrotropin and stimulating corticosterone secretion; theobromine and paraxanthine were less potent, but their own serum concentrations were also lower. One week of once-daily injections of 50 mg/kg of caffeine produced tolerance to its effects on thyrotropin and corticosterone. The lowest caffeine dose to produce tolerance to a 50-mg/kg challenge dose was 25 mg/kg. Adenosine receptor agonists did not affect serum thyrotropin nor did they block the caffeine-induced decrease in serum thyrotropin. Blockade of the hypothermic effect of caffeine did not alter the effect of caffeine on serum thyrotropin. Similarly, the caffeine-induced decrease in serum thyrotropin was additive to the decrease produced by placing rats in a warm environment or to the increase in serum thyrotropin produced by placing them in the cold. Deviating from the stress-like pattern of increased corticosterone and decreased thyrotropin, caffeine did not affect prolactin secretion in ovariectomized rats with or without estrogen pretreatment.