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

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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 (ED50nM). 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+]1, and markedly reduced the rise in [Ca2+]1elicited 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.Ourresults demonstrate that SRIH may inhibit PRL release from GH4C1cells by (1) inhibiting hormone‐sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]1. 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+]1elevation. Since the GH4C1cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems.

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