Effects of histamine H1- and H2-receptor antagonists on thyrotrophin secretion in the rat

The effects of histamine H1- and H2-receptor antagonists on the pituitary-thyroid axis were studied in normal and thyroxine (T4)-treated rats. Acute administration (120 min before the test) of the H2 antagonist cimetidine induced a significant (P less than 0.01) increase in the TSH response to TRH, whereas treatment with histamine (30 min before the test) or with the H1-receptor blocker diphenhydramine (120 min before the test) was without effect. Treatment with cimetidine or ranitidine (another H2-receptor antagonist) for 5 days induced a marked decrease in basal plasma TSH concentrations (P less than 0.01), with no changes in pituitary concentrations of TSH. Plasma prolactin concentrations were similarly decreased by cimetidine (P less than 0.01), though not by ranitidine. Neither antihistaminic altered pituitary prolactin concentrations. Despite decreasing basal concentrations of plasma TSH, cimetidine augmented the response to TRH above baseline values (P less than 0.01) in control rats as well as in animals with T4-induced suppression of plasma TSH. Administration of cimetidine or ranitidine for 5 days was followed by a reduced concentration of plasma T4 and triiodothyronine (T3) (P less than 0.05 and P less than 0.01 respectively), perhaps as a result of the declining plasma TSH levels. These results provide the first evidence for the reduction of plasma TSH concentrations by H2-receptor blockers, and may indicate that histamine can physiologically regulate TSH and prolactin secretion through H2 receptors in the anterior pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)