Augmented Secretion of TSH in Response to TRH After Pre-Treatment With Dexamethasone for Six Days in Rats

Abstract

Serum TSH and corticosterone concentrations were measured in rats given TRH or exposed to short-term cold, as well as in intact rats, after pretreatment with dexamethasone for six days at two different dose levels (25 and 250 \g=m\g/100g body weight). Both doses increased the secretion of TSH in response to TRH whereas cold-induced TSH secretion was not modified by pre-treatment with dexamethasone. In intact rats serum TSH levels did not differ significantly from controls. In all experiments the steroid blocked ACTH secretion. It was also found that administration of TRH produced a rise in serum corticosterone concentrations. Our results support the view that dexamethasone given for six days facilitates TRH stimulation of the pituitary whilst simultaneously inhibiting the secretion of TRH in response to cold.The effect of glucocorticoids on TSH secretion in the rat has been a subject of considerable interest and confusion. Short-term pre-treatment with dexametha¬ sone has been shown to increase the release of TSH from the pituitary in re¬ sponse to TRH (Sakiz 8c Guillemin 1965) and to inhibit cold-induced rises in serum TSH (Ducommun et al. 1966). Other investigators have, however, been unable to confirm these findings (Wilber 8c Utiger 1969;Fortier et al. 1970;Koch et al. 1972). In the light of recent research this inconsistency of results can be understood. It has been shown that the effect of dexamethasone on the secretion of TSH is highly dependent on time schedules used (Brown 8c Hedge 1973Ranta 1975). It is, however, not known how dexamethasone affects 710 The Institute of Physiology, University of Helsinki

Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats

“…A-A saline, o-o 25 (ig of dexamethasone/100 g body weight, •-• 500 ug of dexamethasone/100 g body weight. Differences from the saline-treated group are shown by * P < 0.001, ** P < 0.05. siveness to TRH was inhibited at 3 h and enhanced at 12 h after dexamethasone treatment (Ranta 1975). Thus, dexamethasone may directly affect the pituitary by triggering TSH release or altering the thyrotroph sensitivity to TRH.…”

“…It has been reported that dexamethasone has potentiating and inhibitory effects both on the suprahypophyseal region and pituitary in rats (Brown & Hedge 1973). It has also been reported that in dexamethasone-treated rats the coldinduced TSH response was suppressed and TSH responsiveness to thyrotrophin releasing hormone (TRH) was potentiated (Ranta 1976). Glucocorti¬ coid also has a direct suppressive effect on TSH secretion (Sowers et al 1977).…”

“…There are several reports concerning the effects of glucocorticoid on the hypothalamic-pituitarythyroid axis in rats or human (Migeon et al 1952;Ingbar & Freinkel 1956;Guillemin 1967;Wilber & Utiger 1969;Fortier et al 1970;Nicoloff et al 1970;Brown & Hedge 1973, 1974Chopra et al 1975;Ranta 1975Ranta , 1976Scwinn et al 1976;Pamenter & Hedge 1980). An inverse relationship between thyroid stimulating hormone (TSH) and adrenocorticotrophin has been reported (Guil¬ lemin 1967), but these findings have not been confirmed (Fortier et al 1970;Brown & Hedge 1973).…”