THECAL CELL-GRANULOSA CELL-INTERACTIONS INVOLVE A POSITIVE FEEDBACK LOOP AMONG KERATINOCYTE GROWTH-FACTOR, HEPATOCYTE GROWTH-FACTOR, AND KIT-LIGAND DURING OVARIAN FOLLICULAR DEVELOPMENT
Ja. Parrott et Mk. Skinner, THECAL CELL-GRANULOSA CELL-INTERACTIONS INVOLVE A POSITIVE FEEDBACK LOOP AMONG KERATINOCYTE GROWTH-FACTOR, HEPATOCYTE GROWTH-FACTOR, AND KIT-LIGAND DURING OVARIAN FOLLICULAR DEVELOPMENT, Endocrinology, 139(5), 1998, pp. 2240-2245
Interactions between mesenchymal-derived thecal cells and epithelial-d
erived granulosa cells are essential for follicular development in the
ovary. These mesenchymal-epithelial cell interactions are in part med
iated by keratinocyte growth factor (KGF), hepatocyte growth factor (H
GF), and Kit ligand (KL). This study investigates the hypothesis that
thecal cell-derived growth factors (e.g. KGF and HGF) regulate granulo
sa cell function, and granulosa cell-derived growth factors (e.g. KL)
regulate thecal cell function. Gonadotropin regulation of this cell-ce
ll interaction is also examined. Sensitive quantitative RT-PCR assays
were used to analyze gene expression of KGF, HGF, and KZ, in the ovary
. Thecal cell-derived KGF and HGF stimulated KL expression in bovine g
ranulosa cells. Granulosa cell-derived KL stimulated KGF and HGF expre
ssion in bovine thecal cells. These results suggest that thecal and gr
anulosa cells interact in a positive feedback loop mediated by KGF, KG
F, and KL. Previous studies have suggested that gonadotropins (i.e. FS
H and LH) regulate locally produced growth factor expression in the ov
ary. Treatment of bovine granulosa cells with FSH and hCG ia LH agonis
t) directly stimulated KL expression. The LH agonist hCG was also foun
d to stimulate both KGF and HGF expression in thecal cells. The action
s of gonadotropins on follicular development may in part be indirectly
regulated by KL, KGF, and HGF expression. A novel positive feedback l
oop was identified between thecal cells and granulosa cells that is me
diated by KL, KGF, and HGF. Thecal cell-derived KGF and HGF can stimul
ate granulosa cell-derived KL expression, and KL, in turn, can stimula
te thecal cell-derived KGF and HGF expression. Combined observations s
upport the hypothesis that mesenchymal-epithelial cell interactions be
tween thecal and granulosa cells can play a significant role during ov
arian follicular development and mediate gonadotropin actions.