Relationship Between Steroidogenic Acute Regulatory Protein Expression and Progesterone Production in Hen Granulosa Cells During Follicle Development1статья
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Аннотация:The present studies were conducted to address cellular mech-anisms responsible for regulating steroidogenic acute regulatoryprotein (StAR) expression and progesterone synthesis at matu-rational stages corresponding to both the time of hen follicleselection, as well as before and after the LH surge in preovu-latory follicle granulosa cells. A recently published report hasestablished that mitogen-activated protein (MAP) kinase signal-ing induced by transforming growth factor a (TGFa) treatmentblocks FSH-induced differentiation and StAR expression in cul-tured hen granulosa cells, whereas inhibitors of MAP kinase sig-naling enhance FSH-induced differentiation. The present in vitrostudies demonstrate that in addition to MAP kinase signaling,activation of protein kinase C (PKC) blocks both FSH-inducedStAR expression and the initiation of progesterone productionin prehierarchal follicle granulosa cells, whereas the pharma-cologic inhibitor of PKC, GF109203X, potentiates FSH-inducedStAR expression and, as a consequence, the initiation of pro-gesterone synthesis. Moreover, we demonstrate in granulosacells collected from preovulatory follicles that although an acuteincrease in progesterone production in response to LH treatmentrequires rapid transcription and translation of StAR, the mag-nitude of progesterone production is rate-limited by one or morefactors other than StAR (e.g., the P450 cholesterol side-chainenzyme). Finally, the rapid turnover of StAR protein, such asoccurs following the withdrawal of LH, provides an additionalmechanism for the tight regulation of progesterone productionthat occurs during the hen ovulatory cycle, and explains therapid loss of steroidogenesis in the postovulatory follicle. Insummary, data reported herein support the proposal that para-crine/autocrine factors (including but not necessarily limited toTGFa) prevent premature expression of StAR in prehierarchalfollicle granulosa cells by more than one receptor-mediated sig-naling pathway. Furthermore, subsequent to follicle selectioninto the preovulatory hierarchy, StAR transcription and transla-tion is necessary but not sufficient for the full potentiation ofthe preovulatory surge of serum progesterone.