title: Mouse hypothalamic growth hormone-releasing hormone and somatostatin responses to probes of signal transduction systems.
abstract: Signal transduction mechanisms involved in mouse growth hormone-releasing hormone (GRH) and somatostatin (SRIH) release were investigated using an in vitro perifusion system. Hypothalamic fragments were exposed to depolarizing agents, protein kinase A and C activators, and a calcium ionophore. The depolarizing agents, KCl (60 mM) and veratridine (50 microM), induced similar patterns of GRH and SRIH release. Somatostatin release in response to both agents was twofold greater than that of GRH. Forskolin (10 microM and 100 microM), an adenylate cyclase activator, stimulated both GRH and SRIH release, though with different secretory profiles. The SRIH response was prolonged and persisted beyond removal of the drug from the system, while the GRH response was brief, ending even prior to forskolin removal. Neither GRH nor SRIH were stimulated by 1,9-dideoxy-forskolin (100 microM), a forskolin analog with cAMP-independent actions. A23187 (5 microM), a calcium ionophore, stimulated the release of SRIH to a much greater extent than that of GRH. The GRH and SRIH secretory responses to PMA (1 microM), a protein kinase C activator, were similar, though delayed. The results suggest that 1) GRH and SRIH secretion are regulated by both protein kinase A and C pathways, and 2) depolarizing agents are important for the release of both hormones.
authors.affiliation: Department of Internal Medicine, University of Cincinnati College of Medicine, OH 45267.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: T R
authors.initials: TR
authors.lastname: Downs
authors.forename: L A
authors.initials: LA
authors.lastname: Frohman
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D011189:Potassium Chloride / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013004:Somatostatin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D005576:Colforsin; D000001:Calcimycin; D013004:Somatostatin; D011189:Potassium Chloride; D014701:Veratridine; D013007:Growth Hormone-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate; C047983:1,9-dideoxyforskolin