Cell-to-cell communication in the ovarian follicle: developmental and hormonal regulation of the expression of connexin43.

Abstract

The extensively developed network of cell-to-cell communication in the ovarian follicle is generated by gap junctions. In addition to the transmission of nutrients from the follicular cells to the oocyte, junctional communication in the ovarian follicle mediates the transfer of cAMP, the regulatory signal that maintains the oocyte in meiotic arrest. Luteinizing hormone (LH) interrupts cell-to-cell communication within the ovarian follicle, leading to a decrease in intra-oocyte concentrations of cAMP followed by resumption of meiosis. The developmental and hormonal regulation of the ovarian gap junction protein connexin43 (Cx43) and gene expression throughout folliculogenesis is reviewed in this article. An age-dependent increase in the amount of the Cx43 protein that was accompanied by its phosphorylation in preovulatory follicles has been observed. This protein disappeared after ovulation. The changes in both the amount and phosphorylation state of Cx43 were mimicked by exogenous administration of hormones as follows. Pregnant mare serum gonadotrophin increased Cx43 protein expression with a concurrent induction of its phosphorylation while a further human chorionic gonadotrophin injection resulted in a significant decrease of the protein. Cx43 mRNA showed a similar pattern of expression. In-vitro analysis of isolated ovarian follicles revealed that short time exposure (10 min) to LH stimulates phosphorylation of Cx43 followed by its immediate dephosphorylation, while longer incubations (8 and 24 h) with this hormone result in elimination of the protein. A significant decrease in Cx43 mRNA concentration at 24 h of incubation with LH was observed in these follicles. These results suggest that: (i) the presence of the gap junction protein in the ovary is developmentally regulated; (ii) after sexual maturation, both the amount of the Cx43 ovarian gap junction protein and its phosphorylation state are subjected to regulation by gonadotrophins; (iii) the LH-induced gating mechanism of the gap junctions in rat ovarian follicles is comprised of two steps: the immediate response is represented by a change in the phosphorylation state of the Cx43 protein, and the later response is manifested by a reduction of Cx43 protein concentration, due to attenuation of its gene expression.