{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:41:02Z","timestamp":1771494062159,"version":"3.50.1"},"reference-count":64,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In goldfish, 2 endogenous GnRH isoforms, GnRH2 and GnRH3, are released at the pituitary and directly stimulate LH and GH release using the same population of GnRH receptors (GnRHRs) but with GnRH-specific transduction mechanisms. Previously, we have shown that phosphoinositide 3-kinases (PI3Ks) mediate GnRH2- and GnRH3-stimulated LH and GH release. Among the 3 classes of PI3Ks, class I PI3Ks are the best characterized and consist of 4 110-kDa catalytic isoforms (p110\u03b1, p110\u03b2, p110\u03b3, and p110\u03b4). Importantly, p110\u03b2 and p110\u03b3, but not p110\u03b1 or p110\u03b4, can be directly activated by the G\u03b2\u03b3 heterodimer of G\u03b1\u03b2\u03b3 protein complexes. In the present study, we examined the expression of class I PI3K isoforms and the effects of selective inhibitors of p110\u03b1, p110\u03b2, p110\u03b3, and p110\u03b4 catalytic activity on basal, as well as acute, GnRH2- and GnRH3-stimulated LH and GH release responses using primary cultures of dispersed goldfish pituitary cells in column perifusion. Results demonstrate that p110\u03b3 and p110\u03b4 are involved in the control of basal LH and GH release, whereas p110\u03b1 and p110\u03b2 only regulate basal LH secretion. However, p110\u03b2 and p110\u03b3 both participated in GnRH3- and GnRH2-stimulated GH release, whereas p110\u03b2 and p110\u03b3 mediated GnRH2- and GnRH3-induced LH release responses, respectively. GnRH2- and GnRH3-stimulated LH release, as well as GnRH3-elicited GH release, also required p110\u03b4. These results constitute the first evidence for the differential involvement of class I PI3K catalytic subunits in GnRH actions, in general, and suggest that GnRH2 and GnRH3 binding to GnRHRs can bias the activation of class I PI3K signaling to mediate hormone release responses in 2 distinct pituitary cell types. The involvement of both class IA and IB PI3Ks implicates G\u03b2\u03b3 subunits, as well as other known regulators of class I PI3Ks, as important components of GnRHR-mediated responses that could influence GnRH-selective signaling in other cell types.<\/jats:p>","DOI":"10.1210\/en.2014-1640","type":"journal-article","created":{"date-parts":[[2014,10,24]],"date-time":"2014-10-24T17:14:05Z","timestamp":1414170845000},"page":"218-230","source":"Crossref","is-referenced-by-count":9,"title":["Ligand-Selective Signal Transduction by Two Endogenous GnRH Isoforms Involves Biased Activation of the Class I PI3K Catalytic Subunits p110\u03b2, p110\u03b3, and p110\u03b4 in Pituitary Gonadotropes and Somatotropes"],"prefix":"10.1210","volume":"156","author":[{"given":"Joshua G.","family":"Pemberton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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