PMID- 12578538 OWN - NLM STAT- MEDLINE DCOM- 20030429 LR - 20191210 IS - 1470-1626 (Print) IS - 1470-1626 (Linking) VI - 125 IP - 2 DP - 2003 Feb TI - Steroidogenic responses of pig corpora lutea to insulin-like growth factor I (IGF-I) throughout the oestrous cycle. PG - 241-9 AB - This study was designed to investigate the roles of insulin-like growth factor I (IGF-I), IGF-type I receptor (IGF-IR) and IGF-binding proteins (IGFBPs) in regulating progesterone secretion by pig corpora lutea during the oestrous cycle, and the signal transduction pathways involved in mediating the steroidogenic actions of IGF-I. Corpora lutea were collected on days 4, 7, 10, 13 and 15 or 16 of the oestrous cycle, enzyme dissociated and the luteal cells were cultured for 24 h in Medium 199 with IGF-I (0-100 ng ml(-1)), long R(3)-IGF-I (0-100 ng ml(-1)), anti-IGF-I (Sm 1.2B; 0-10 microg ml(-1)), anti-IGF-IR (alphaIR3; 0-2 microg ml(-1)), or IGF-I signal transduction pathway inhibitors (phosphatidylinositol (PI)-3-kinase: 100 nmol Wortmannin l(-1) and 10 micromol LY 294002 l(-1); MAP kinase: 50 micromol PD 98059 l(-1)) to investigate their effects on IGF-I (100 ng ml(-1)) stimulated progesterone secretion. Pig luteal cells displayed dose-dependent responses to IGF-I and long R(3)-IGF-I on days 4 and 7 of the oestrous cycle, but not on days 10-16. There was no difference in the ED(50) or V(max) (maximal response) values between IGF-I and long R(3)-IGF-I. Neither anti-IGF-I nor anti-IGF-IR had significant effects on progesterone secretion, at any dose or day. Wortmannin and LY 294002 blocked IGF-I stimulated progesterone secretion, but PD 98059 was without effect. Finally, IGF-I (6 microg) infused into the ovary on day 7 in vivo significantly increased progesterone secretion within 45 min of infusion. The conclusions of this study are: (1) IGF-I has steroidogenic actions only on 'young' (days 4-7) pig corpora lutea; (2) endogenous IGF-I and IGFBP are insufficient to modulate progesterone secretion in vitro; and (3) the steroidogenic actions of IGF-I are mediated via PI-3-kinase. FAU - Miller, E A AU - Miller EA AD - Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. FAU - Ge, Z AU - Ge Z FAU - Hedgpeth, V AU - Hedgpeth V FAU - Gadsby, J E AU - Gadsby JE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Reproduction JT - Reproduction (Cambridge, England) JID - 100966036 RN - 0 (Androstadienes) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (long R(3)-insulin-like growth factor-I) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 4G7DS2Q64Y (Progesterone) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.10.1 (Receptor, IGF Type 1) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) RN - XVA4O219QW (Wortmannin) SB - IM MH - Androstadienes/pharmacology MH - Animals MH - Cells, Cultured MH - Chromones/pharmacology MH - Corpus Luteum/drug effects/*metabolism MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Estrus/*metabolism MH - Female MH - Flavonoids/pharmacology MH - Follicular Phase MH - Insulin-Like Growth Factor I/*analogs & derivatives/metabolism/*pharmacology MH - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors MH - Morpholines/pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Progesterone/*metabolism MH - Receptor, IGF Type 1/antagonists & inhibitors MH - *Signal Transduction MH - Sus scrofa/*metabolism MH - Wortmannin EDAT- 2003/02/13 04:00 MHDA- 2003/04/30 05:00 CRDT- 2003/02/13 04:00 PHST- 2003/02/13 04:00 [pubmed] PHST- 2003/04/30 05:00 [medline] PHST- 2003/02/13 04:00 [entrez] PST - ppublish SO - Reproduction. 2003 Feb;125(2):241-9.