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Endocrinology, Vol 117, 2170-2175, Copyright © 1985 by Endocrine Society
ARTICLES |
SW Shyr and CE Grosvenor
The histidyl-proline-diketopiperazine (cyclo-his-pro) metabolite of TRH inhibited the transformation of prereleasable PRL within the anterior pituitary and as a consequence, the normal rise in plasma PRL levels when injected before suckling. The dose (400 ng) was administered five times at 1-min intervals. PRL suppression was similar to that resulting from dopamine injected at the same rate. Combined injections of cyclo- his-pro and dopamine, each at the 400 ng/min for 5 min rate, provoked a greater inhibition of PRL than did either alone. Neither cyclo-his-pro nor dopamine inhibited the suckling-induced release of PRL in rats whose PRL had previously been transformed by a short (10-min) period of suckling. The stimulatory effects of iv administered domperidone (0.005 or 0.01 mg/rat) and haloperidol (0.2 mg/rat) upon PRL transformation and release in the lactating rat were substantially reduced by cyclo- his-pro in a dose-related fashion over a range of doses from 200-800 ng/min for 5 min. These results demonstrate that cyclo-his-pro inhibits PRL secretion in the lactating rat after suckling, primarily through inhibition of the transformation phase, and that the inhibitory mechanism may involve an interaction with dopamine.
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