1188
document
Effects of pyridostigmine and naloxone on the abnormal TSH response to TRH during starvation in humans . BACKGROUND Starvation is associated with a blunted TSH response to thyrotropin-releasing hormone ( TRH ) ( peak minus baseline < 5 mIU/L ) , despite basal TSH and thyroid hormone levels within the normal range . In light of the inhibitory effect of somatostatin on TSH secretion , we examined whether this condition is caused by an increased hypothalamic somatostatinergic tone in starving subjects . The possible involvement of endogenous opioids in the mechanism underlying the abnormal TSH response to TRH was also evaluated . METHODS The TSH response to TRH ( 25 micrograms in an intravenous bolus ) , serum total and free T4 and T3 levels , and 24-hour urinary-free cortisol levels were measured in 28 normal men ( age 27-35 years ) within 10 % of their ideal body weight . They were randomly divided into 4 groups of 7 . In 21 subjects ( groups 1 , 2 , and 3 ) , TRH tests were performed after an overnight ( 8 hours ) fast , placebo administrations ( control test ) , and after prolonged ( 56 hours ) starvation . TRH tests after prolonged starvation were performed either after placebos ( in all subjects ) or the administration of pyridostigmine ( 180 mg orally ) ( in 7 subjects , group 1 ) ; naloxone ( 0.8 mg in an i.v . bolus injection ) ( in 7 subjects , group 2 ) ; or the combination of pyridostigmine and naloxone ( in 7 subjects , group 3 ) . The remaining 7 subjects ( group 4 ) were tested at weekly intervals with TRH plus placebo , TRH plus naloxone , TRH plus pyridostigmine , and TRH plus naloxone plus pyridostigmine after a fasting period of 8 hours . RESULTS In all subjects of groups 1 , 2 , and 3 , TRH-induced TSH rise was significantly lower after prolonged starvation than after overnight fast . Neither pyridostigmine nor naloxone , given alone , changed the basal levels of TSH and the TSH response to TRH after prolonged starvation . In contrast , the concomitant administration of naloxone and pyridostigmine significantly enhanced the TRH-induced TSH rise . After overnight fasting , naloxone administration in group 4 subjects did not change the TSH response to TRH , whereas pyridostigmine significantly enhanced the TSH response to TRH . When naloxone was given together with pyridostigmine and TRH the TSH response was similar to that observed in the TRH plus pyridostigmine test . CONCLUSIONS These data indicate that naloxone-sensitive endogenous opioids exert an inhibitory effect on the cholinergic stimulatory control of TSH secretion during prolonged starvation . This suggests that an enhanced hypothalamic somatostatinergic activity is involved in the mechanism underlying the reduced TSH response to TRH .
1189
Intervention_Pharmacological
pyridostigmine
1190
Intervention_Pharmacological
naloxone
1191
Intervention_Pharmacological
TRH
1192
Intervention_Control
placebo
1193
Intervention_Control
placebos
1194
Intervention_Pharmacological
pyridostigmine
1195
Intervention_Pharmacological
naloxone
1196
Intervention_Pharmacological
pyridostigmine and naloxone
1197
Intervention_Pharmacological
TRH
1198
Intervention_Control
placebo
1199
Intervention_Pharmacological
TRH plus naloxone
1200
Intervention_Pharmacological
TRH plus pyridostigmine
1201
Intervention_Pharmacological
TRH
1202
Intervention_Pharmacological
naloxone
1203
Intervention_Pharmacological
pyridostigmine
1204
Intervention_Pharmacological
pyridostigmine
1205
Intervention_Pharmacological
naloxone
1206
Intervention_Pharmacological
pyridostigmine
1207
Intervention_Pharmacological
TRH
1208
Outcome_Physical
abnormal TSH response to TRH during starvation
1209
Outcome_Physical
blunted TSH response
1210
Outcome_Physical
thyrotropin-releasing hormone ( TRH )
1211
Outcome_Physical
hypothalamic somatostatinergic tone
1212
Outcome_Physical
abnormal TSH response to TRH
1213
Outcome_Physical
TSH response to TRH
1214
Outcome_Physical
serum total and free T4 and T3 levels
1215
Outcome_Physical
24-hour urinary-free cortisol levels
1216
Outcome_Other
TRH tests after prolonged starvation
1217
Outcome_Physical
TRH-induced TSH rise
1218
Outcome_Physical
basal levels of TSH
1219
Outcome_Physical
TSH response to TRH after prolonged starvation
1220
Outcome_Other
cholinergic stimulatory control of TSH secretion
1221
Participant_Condition
during starvation in humans .
1222
Participant_Condition
starving subjects
1223
Participant_Sample-size
28
1224
Participant_Condition
normal
1225
Participant_Age
age 27-35 years