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Dopamine Withdrawal and Addition of Thyrotropin-Releasing Hormone Stimulate Membrane Translocation of Protein Kinase-C and Phosphorylation of an Endogenous 80K Substrate in Enriched Lactotrophs^*

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California School of Medicine San Francisco, California 94143
Departamento de Fisiologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico 04510 Mexico City, Mexico
the Department of Zoology, University of Wisconsin Madison, Wisconsin 53706

Address all correspondence and requests for reprints to: Gonzalo Martinez de la Escalera, Ph.D., Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, P.O. Box 70228,04510 Mexico City, Mexico.

Abstract

The biochemical mechanisms underlying the direct stimulatory action of dopamine (DA) withdrawal on PRL release and on the potentiation of TRH stimulation are not known. These actions can be mimicked by pretreatment of lactotrophs with the protein kinase-C (PKC) activator 12-0-tetradecanoyl-phorbol-13-acetate. Previous studies have shown that administration of TRH or withdrawal of DA stimulates polyphosphoinositide breakdown, although to different degrees. We have tested whether the acute withdrawal of DA activates PKC and determined if the prior removal of DA modifies the activation of PKC by TRH. Primary cultures of dispersed anterior pituitaries from estradiol-treated rats consisting of approximately 80% lactotrophs were maintained overnight in 500 nM DA. Activation of PKC was assayed immunochemically as translocation of PKC to a membrane fraction and by in situ phosphorylation of an acid-soluble heat-stable 80K substrate. Acute withdrawal of DA induced translocation of immunoreactive PKC to the membrane fraction (25-250%) and enhanced phosphorylation (40-100%) of an 80K protein. These effects were detected within 5-15 sec of DA withdrawal and were prolonged (10-30 min). TRH induced a rapid and transient activation of both parameters. The duration and magnitude of the action of TRH were increased by prior removal of DA. These results are consistent with a role for PKC activation in transduction of the stimulation of PRL release by the withdrawal of DA. The longer lasting activation of PKC may explain at least in part the potentiation of the PRL-releasing action of TRH by the withdrawal of DA.

Footnotes

^* This work was supported by NIH Grants HD-08924 (to R.I.W.) and DK-25861 (to T.F.J.M.) and the Mellon Foundation.

Received March 17, 1989.

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