Figure 3. A schematic the interactions of the local organizational factors and impact factors that operative in preovulatory, ovulatory, and ovulating follicles. The transition of small antral follicles to preovulatory follicles is dependent on both the local organizational factors such as IGF-1 and the external impact factors FSH and LH. LH regulates theca cell differentiation. FSH dictates specific changes in granulosa cell gene expression, enhanced proliferation, and the formation of the antrum that clearly separates the oocyte-cumulus component of the follicle from the mural layer of endocrine cells. FSH and IGF pathways interact to control the expression/activation of specific kinase cascades. Two kinases in these cascades are Sgk and PKB, which activate forkhead transcription factors, FKRH, and other cell survival pathways, such as the expression and movement of the glucose transporter Glut-4 to the plasma membrane (see text for further discussion). The LH surge terminates the follicular program of gene expression in granulosa cells and turns on genes controlling cumulus expansion (COX-2, HAS, TSG-6), ovulation (PR, ADAMTS-1), and luteinization (C/EBPß and Egr-1). LH acts directly on granulosa cells and theca cells but likely acts indirectly on the cumulus cells. For example, LH may act on granulosa cells (heavy red arrow) to stimulate the synthesis of a product(s) that is released and impacts cumulus cell function leading to the induction of COX-2 and TSG-6. One oocyte-derived factor that has been implicated in cumulus cell expression of COX-2 is GDF-9. Because GDF-9 is present in ooctyes at all stages of follicular growth, LH may stimulate the production of a specific protease to activate latent GDF-9. COX-2 in turn appears critical for the expression of TSG-6 (Ochsner, S., and J. S. Richards, unpublished observations). Oocytes of ovulating follicles also express mater, a maternal gene product necessary for embryogenesis (117 ). In the mural granulosa cells, LH acts to induce other genes involved in the ovulation process (PR, ADAMTS-1, and Cathepsin L). Genes involved in the establishment of luteinization include C/EBPß, Egr-1 and p27kip1. Once terminal differentiation is complete, luteal cells express steroidogenic enzymes (P450scc and StAR),transcription factors (JunD, Fra2, ERα) as well as Sgk, a kinase in the PI3-K/PDK1 pathway in a constitutive manner.
Source: Endocrinology 2001 Jun;142(6):2184-93
Edited by Aldo Campana,