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.