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A Novel Function of Prolactin-Releasing Peptide in the Control of Growth Hormone via Secretion of Somatostatin from the Hypothalamus¹

Departments of Anatomy and Neurobiology (N.I., M.T., Takan Y., Y.I.), Anesthesiology (K.K.), Obstetrics and Gynecology (Y.K.), Kyoto Prefectural University of Medicine, Kyoto 602-0841; Department of Anatomy (Y.T.), Osaka Dental University, Osaka 573-1121; Discovery Research Laboratories I (H.M., N.S., S.H.), Ibaraki 300-4293, Discovery Research Laboratories III (Y.M., Takan Y.), Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka 532-8686, Japan

Address all correspondence and requests for reprints to: Yasuhiko Ibata, M.D., Ph.D., Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi-Hiokoji, Kamikyo 602-0841, Japan. E-mail: yibata{at}basic.kpu-m.ac.jp

The present study examined a novel function of PRL-releasing peptide (PrRP) on the neuroendocrine. PrRP-immunoreactive nerve fibers and nerve terminals were located in the vicinity of the somatostatin (SOM)-neurons in the hypothalamic periventricular nucleus (PerVN). Immuno-electron microscopy revealed that PrRP-immunoreactive nerve terminals made synaptic contacts with nonimmunoreactive neuronal elements in the PerVN. Intracerebroventricular (icv) administration of PrRP induced immediate early gene, NGFI-A, in SOM-neurons in the PerVN. Double-labeling in situ hybridization showed that some parts of SOM-neurons in the PerVN expressed PrRP receptor messenger RNA. Therefore, some parts of SOM-neurons in the PerVN are considered to be directly innervated by PrRP via PrRP receptor. In addition to the above morphological characteristics, icv administration of PrRP decreased plasma GH levels. Such inhibitory effects of PrRP on the secretion of GH from the anterior pituitary were diminished by depletion or neutralization of SOM. From these findings it was strongly suggested that SOM-neurons respond to PrRP and secrete SOM into the portal vessels and thus inhibit GH secretion from the anterior pituitary.

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