AJP - Endocrinology and Metabolism, Vol 239, Issue 6 468-E473, Copyright © 1980 by American Physiological Society
Effect of diphenylhydantoin on hypothalamic-pituitary-thyroid function in the rat
T. Theodoropoulos, S. L. Fang, F. Azizi, S. H. Ingbar, A. G. Vagenakis and L. E. Braverman
Chronic diphenylhydantoin (DPH) administration (5 mg x 100 g body wt-1 x
day-1) to the normal rat is associated with a decrease in the serum
thyroxine (T4) and triiodothyronine (T3) concentrations without an
appropriate rise in the serum thyrotropin (TSH) concentration, suggesting a
possible direct effect of DPH on TSH secretion. To further study this
possibility, DPH was administered chronically to thyroidectomized,
hypothyroid rats. In the hypothyroid rats treated chronically with DPH,
serum TSH did not increase, pituitary TSH content was significantly
decreased, and the serum TSH response to thyrotropin-releasing hormone
(TRH) was decreased compared to that of diluent-treated, hypothyroid rats.
Hypothalamic TRH content was similar in DPH and diluent-treated rats. These
findings suggest that DPH suppresses pituitary TSH secretion, probably as a
thyroid hormone agonist. The effect of a single large dose of DPH (20
mg/100 g body wt) administered to thyroidectomized rats also decreased
serum tSH but, in contrast to the findings in chronically treated rats,
hypothalamic TRH and pituitary TSH content and the serum TSH responses to
TRH were increased. These differences may be due to the acute inhibitory
effect of a large dose of DPH on hypothalamic TRH release. Furthermore,
because the effect of thyroid hormone on regulating pituitary TSH synthesis
and release is dose and time dependent, the effect of DPH as a thyroid
hormone agonist on pituitary TSH dynamics may also be variable.
