The TSH, T4, T3 and prolactin responses to consecutive infusions of a potent and stabilized thyrotrophin releasing hormone analogue, RX77368, in man.
The endocrine manifestations of a stabilized thyrotrophin releasing hormone (TRH) analogue, RX77368, have been investigated in six male volunteers. Infusions were given on two occasions, with a 5-day interval between infusions. On the second exposure to RX77368, there was a significant reduction in the TSH response, despite normal basal T3 and T4 levels, while the response of prolactin to RX77368 was unaltered. Domperidone administered during the infusion of RX77368 caused a further elevation of prolactin levels, whilst TSH levels were unchanged. This study shows the differential regulation of thyrotrophs and lactotrophs in response to stimulation by a TRH analogue, and shows, for the first time, down-regulation of the TSH response in vivo, in the presence of normal peripheral thyroid hormone levels. The T3 response to infusions of RX77368 was less than to a bolus injection of TRH, despite a greater TSH response to the analogue, suggesting impaired biological activity of TSH released in response to an infusion of the analogue.
Eckland
D J
DJ
Charing Cross Medical School, Westminster Hospital, London, U.K.
Lightman
S L
SL
D000328:Adult; D002490:Central Nervous System / Q000187:drug effects; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018025:Receptors, Thyrotropin-Releasing Hormone; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011388:Prolactin; D013972:Thyrotropin; D013974:Thyroxine; D011761:Pyrrolidonecarboxylic Acid