title: Somatostatin inhibits prolactin secretion by multiple mechanisms involving a site of action distal to increased cyclic adenosine 3',5'-monophosphate and elevated cytosolic Ca2+ in rat lactotrophs.
abstract: The release of prolactin (PRL) from a clonal cell-line of anterior pituitary cells (GH4C1) was inhibited by somatostatin (SRIH) in a dose-dependent manner (ED50 nM). The inhibition (20% of control levels) was detectable within 50 s and maximal within 90 s. Thyroliberin (TRH) enhancement of PRL secretion was biphasic. SRIH inhibited both phases equally. Ionomycin in combination with the phorbol ester, TPA, mimics the TRH-elicited PRL release, and SRIH partly inhibited this effect. SRIH had no effect on TRH-stimulated formation of inositol trisphosphate, and only small effects on TRH-activated adenylate cyclase. Vasoactive intestinal peptide (VIP) and forskolin stimulated cAMP formation and PRL release potently. SRIH inhibited both effects of VIP and forskolin, and there was a close correlation between the inhibition of PRL secretion and cAMP accumulation. 8-Bromo-cAMP enhanced PRL release, an effect that was also partly reduced by SRIH. The Ca2+ channel activator, BAY-K-8644 and high extracellular K+ increased PRL release, and SRIH caused a partial reduction in the release response to both secretagogues. SRIH lowered [Ca2+]i, and markedly reduced the rise in [Ca2+]i elicited by TRH, VIP and K+. SRIH did not influence the Ca2+ spikes recorded in Na+-free solution, and had no effect on the TRH-induced membrane potential changes. Our results demonstrate that SRIH may inhibit PRL release from GH4C1 cells by (1) inhibiting hormone-sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]i. None of these effects is, however, sufficient to explain all the effects of SRIH, suggesting that SRIH also exerts a major action at a step subsequent to cAMP accumulation and [Ca2+]i elevation. Since the GH4C1 cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems.
authors.affiliation: Hormone Laboratory, Aker Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Bjøro
authors.forename: B C
authors.initials: BC
authors.lastname: Ostberg
authors.forename: O
authors.initials: O
authors.lastname: Sand
authors.forename: P A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: E
authors.initials: E
authors.lastname: Penman
authors.forename: J O
authors.initials: JO
authors.lastname: Gordeladze
authors.forename: J G
authors.initials: JG
authors.lastname: Iversen
authors.forename: K M
authors.initials: KM
authors.lastname: Gautvik
authors.forename: E
authors.initials: E
authors.lastname: Haug
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000494:pharmacology*
chemical_list: D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D013004:Somatostatin; D011388:Prolactin; D000242:Cyclic AMP; D002118:Calcium