THE THYROTROPIN-RELEASING HORMONE-LIKE PEPTIDES PGLU-PHE-PRO AMIDE AND PGLU-GLU-PRO AMIDE INCREASE PLASMA TRIIODOTHYRONINE LEVELS IN THE MOUSE - THE ACTIVITY IS SENSITIVE TO TESTOSTERONE

Three naturally occurring peptides, pGlu-Glu-Pro amide, pGlu-Phe-Pro a mide and pGlu-Gln-Pro amide, with similar structures to thyrotropin re leasing hormone (TRH) have recently been identified but no studies of their in vivo activities have been reported previously. We describe he re the ability of pGlu-Phe-Pro amide and pGlu-Glu-Pro amide to influen ce thyroid status. Subcutaneous administration of these 'TRH-like' pep tides in male and female CD1 mice led to increased levels of triiodoth yronine (T3) and to a lesser extent tetraiodothyronine (T4) in the cir culation. pGlu-Phe-Pro amide was more potent than pGlu-Glu-Pro amide; it exhibited a similar potency to pGlu-His-Pro amide (TRH). pGlu-Phe-P ro amide, pGlu-Glu-Pro amide and TRH produced significantly greater ef fects in the female than in the male. Castration of male mice led to i ncreased activities, with potencies comparable to those seen in the fe male, in contrast treatment of female mice with testosterone resulted in reduced activities, similar to those observed in the control male. The effects of potassium deprivation on the activities of the TRH-like peptides were also investigated. This diet, which results in decrease d testosterone levels in the male, led to increased activities of the TRH-like peptides and TRH, approaching the potencies observed in the f emale. The results demonstrate that the TRH-like peptides pGlu-Phe-Pro amide and pGlu-Glu-Pro amide which occur naturally in the thyroid gla nd exhibit biological activity in influencing thyroid status in vivo. The activities are sensitive to testosterone. (C) 1998 Elsevier Scienc e B.V. All rights reserved.