A study of the effect of the thyrotropin-releasing hormone metabolite, histidyl-proline diketopiperazine, on prolactin secretion in vivo.
TRH, a PRL secretogogue, is metabolized to histidyl-proline diketopiperazine (HPD) in brain and plasma. HPD has been reported to inhibit PRL secretion in vitro. In the present study, intravascular pulse injections or infusions of HPD were carried out in the rat to determine whether HPD affected 1) TRH-induced PRL secretion, 2) the PRL proestrous surge, 3) the PRL surge in the ovariectomized, estrogen-primed rat and 4) pimozide-induced hyperprolactinemia. HPD had no effect on TRH-induced PRL secretion in estrogen-primed male rats when administered in molar ratios of 1:1.5 to 1:150 (TRH:HPD). The infusion of 1 microgram/min HPD for 360 min to rats before and during the proestrous PRL surge did not inhibit or augment PRL secretion, nor was there any influence of pulse injections of HPD on PRL secretion during the proestrous surge. HPD did not influence spontaneous PRL surges in the ovariectomized estrogen-primed rat. Finally, HPD, given with pimozide and again 2 days later, did not influence the PRL surge after pimozide administration or the elevated serum PRL concentrations noted 2 days after pimozide treatment. Despite the promising in vitro data demonstrating that the TRH metabolite, HPD, has PRL inhibitory factor activity, this study does not support the concept that HPD is a physiological PRL inhibitory factor.
D000818:Animals; D002369:Castration; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010868:Pimozide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D011359:Proestrus; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism
D010456:Peptides, Cyclic; D010879:Piperazines; D010868:Pimozide; D004958:Estradiol; D011388:Prolactin; D013972:Thyrotropin; C015924:histidyl-proline diketopiperazine