Effects of Pituitary Adenylate Cyclase-Activating Polypeptide in the Pituitary: Activation of Two Signal Transduction Pathways in the Gonadotrope-Derived αT3-1 Cell Line

E. Schomerus, A. Poch, R. Bunting, W. T. Mason, C. A. Mcardle

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122 Scopus citations

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is thought to play a hypophysiotropic role, but little is known of the identity of PACAP-stimulated cells in the pituitary, the nature of the PACAP receptors on specific cell types, and the effector systems for these receptors. Here we describe the effects of PACAP in αT3-1 cells, a gonadotrope-derived cell line. In these cells, PACAP38 causes concentration-dependent increases in cAMP accumulation (EC50, 3 nM), [3H]inositol phosphite ([3H]IP) production (EC50, 20 nM), and the cytosolic Ca2+ concentration. The Ca2+ response is biphasic and is sustained only in Ca2+-containing medium. Intact αT3-1 cells possess a single class of [125I]PACAP27-binding sites (Kd, 3.3 nM; binding capacity, 35 fmol/106 cells). The rank orders of potencies for stimulation of cAMP and [3H]IP production and for inhibition of [125I] PACAP27 binding by three related peptides are identical (PACAP38 = PACAP27 ≫ vasoactive intestinal peptide). In addition to stimulation of LH release from primary cultures of rat pituitary cells and [3H] IP accumulation in αT3-1 cells, PACAP38 synergizes with low GnRH concentrations in the production of these effects. Moreover, long term exposure to PACAP38 stimulates [3H]thymidine incorporation and increases steady state levels of the gonadotropin α-subunit in αT3-1 cells. We conclude that αT3-1 cells possess type I PACAP receptors which mediate the observed effector system responses, and demonstration of the effects of PACAP on this gonadotrope-derived cell line provides further evidence that gonadotropes are direct targets for PACAP action. The data imply that stimulation of phospholipase-C by PACAP is responsible (at least in part) for the observed increase in cytosolic Ca2+, which, in turn, probably mediates the effects of PACAP on LH release. We suggest, however, that in gonadotropes, the effects of PACAP on cell replication and gonadotropin synthesis may prove more important than the peptide's modest effects on LH release. (Endocrinology 134: 315-323, 1994).

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalEndocrinology
Volume134
Issue number1
StatePublished - Jan 1994
Externally publishedYes

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