Thyrotropin and prolactin responses to thyrotropin-releasing hormone: influence of fasting- and insulin-induced changes in glucose metabolism

It has been reported that prolonged fasting inhibits the response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) in normal persons. To explore possible mechanisms behind this reduced TSH responsiveness and also to see whether dietary factors influence prolactin (PRL) responsiveness, six nonobese volunteers were intravenously injected with a small dose of TRH (25 μg) after three different fasting periods: an 8-hour overnight fast, a 56-hour fast supplemented with oral administration of glucose (4 g/kg/56 h yielding 16 kcal/kg/56 h), and a 56-hour fast supplemented with oral administration of an equicaloric amount of an amino acid (AA) mixture (4 g/kg/56 h) containing 17 different amino acids. The dose of TRH raised the PRL level from 14 ± 2 to 58 ± 8 ng/ml after the overnight fast. Similar PRL responses were obtained after the two prolonged fasting periods. The TRH also raised the TSH level from 1.0 ± 0.0 to 5.2 ± 0.8 μU/ml after the overnight fast. Prolonged fasting with glucose supplementation had no significant effect on this TSH responsiveness, nor did it change the basal blood glucose level. In contrast, prolonged fasting with AA supplementation not only reduced TSH responsiveness by 47 ± 7% (P < 0.002), it also lowered the basal blood glucose level from 4.2 ± 0.1 to 3.5 ± 0.2 mmol/L (P < 0.002). In an additional six normal subjects who fasted overnight, 25 μg TRH was injected intravenously on two occasions: after intravenous infusion of insulin, and after intravenous infusion of saline. The insulin induced market hypoglycemia (1.8 ± 0.1 mmol/L) in 30 ± 3 minutes, whereas saline, infused over a similar time period, had no significant influence on the blood glucose level. When PRL responsiveness was measured during the insulin-induced hypoglycemia, it was found to be increased by 56 ± 15% (P < 0.02). The corresponding TSH responsiveness was decreased by 18 ± 6% (P < 0.05). These results imply that an adequate glucose delivery to pituitary thyrotrophs might be a prerequisite for normal TSH responsiveness. They also show that changes in glucose utilization affect lactotrophs and thyrotrophs differently.