Physiological Role of Theca-Granulosa Cell Interactions in Controlling Ovarian Follicular Development and Atresia

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1. We have investigated the possible role of theca and granulosa cell interaction in the control of follicular maturation and atresia during bovine ovarian follicular developmentusng a co-culture system in which granulosa and theca cells were grown on oppositesides of a collagen membrane. We have already demonstrated the following facs.(1) Granulosa-theca cell interaction is a major follicular constituent in the control of follicular cell differentiation; theca cells secrete factor(s) inhibiting the differentiation of the immature granulosa cells while promoting that of the matured ones and that granulosa cells secrete factor(s) promoting both the differentiation and growth of thecacells throughout the follicular maturation process.(2) Thecal factor(s) control the apoptosis of granulosa cells; inhibit the apoptosis of granulosa cells at the early and late stage of follicular development. Susceptibility of granulosa cells to apoptosis decreases as follicles grow.2. In the second series of the study, we established human granulosa cell lines by triply transfected with SV40 DNA, Ha-ras oncogene and the temperature sensitive mutant of p53(p53-val135). Using this cell-line (HO-23), it was confirmed that glucocorticoids and extracellular matrix(ECM) enhanced P4 production while bFGF and phorbol ester TPA suppressed it, that glucocorticoids, ECM and bFGF inhibited p53-induced apoptosis of HO-23 cells while TPA enhanced it, and that apoptosis at early stage does not interrupt steroidogenesis.