Factors Involved in the Attenuation of the TSH Response to a Second Injection of TRH in the Rat

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Abstract
The attenuation of thyrotropin (TSH) responsiveness to a second injection of thyrotropin-releasing hormone (TRH) was studied in adult female rats. This attenuation occurs using submaximal doses of TRH and it is proportional to the dose of the first stimulus within the range of 0-1,250 ng TRH/100 g BW. The magnitude of the attenuation varies inversely with the interstimulus interval whether the TRH is administered intravenously or directly into the anterior pituitary. This diminished responsiveness is independent of stress or anesthesia, and it is not due to negative feedback by thyroid hormones released in response to the initial TRH stimulation. Exogenous rat TSH given to mimic the response to TRH also results in attenuation, and it is suggested that TSH is at least in part responsible for the attenuation observed after TRH administration.