Insulin-like growth factor-I augments prolactin and inhibits growth hormone release through distinct as well as overlapping cellular signaling pathways.
We recently discovered a new role for insulin-like growth factor-I (IGF-I) as a specific and direct stimulator of prolactin (PRL) release in addition to its recognized function as an inhibitor of growth hormone (GH) release and synthesis. Little is known of the mechanisms that transduce the actions of IGF-I on PRL and GH release in vertebrates. The present study was undertaken to determine the cellular pathways that mediate the disparate actions of IGF-I on PRL and GH release in hybrid striped bass (Morone saxatilis X M. chrysops). When regulating cellular function, IGF-I may activate two primary pathways, phosphatidylinositol 3-kinase (PI 3-K) and mitogen-activated protein kinase (MAPK). The specific MAPK inhibitor, PD98059, blocked IGF-I-evoked PRL release as well as GH release inhibition over an 18-20-h incubation. LY294002, a specific PI 3-K inhibitor, overcame IGF-I's inhibition of GH release but was ineffective in blocking PRL release stimulated by IGF-I. These studies suggest IGF-I disparately alters PRL and GH by activating distinct as well as overlapping signaling pathways central for mediating actions of growth factors on secretory activity as well as cell proliferation. These results further support a role for IGF-I as a physiological regulator of PRL and GH.
Fruchtman
S
S
Department of Zoology, North Carolina State University, Box 7617, Raleigh, NC 27695-7617, USA.
Gift
B
B
Howes
B
B
Borski
R
R
D000818:Animals; D001492:Bass / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011388:Prolactin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology
D002867:Chromones; D005419:Flavonoids; D013006:Growth Hormone; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011388:Prolactin; D020123:Sirolimus; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one