Cell-to-cell communication in the ovarian follicle: developmental and hormonal regulation of the expression of connexin43. 1998

I Granot, and N Dekel
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

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.

UI MeSH Term Description Entries
D011499 Protein Processing, Post-Translational Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility. Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D005260 Female Females
D006080 Ovarian Follicle An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS. Graafian Follicle,Atretic Follicle,Ovarian Follicles,Atretic Follicles,Follicle, Atretic,Follicle, Graafian,Follicle, Ovarian,Follicles, Atretic,Follicles, Graafian,Follicles, Ovarian,Graafian Follicles
D006728 Hormones Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018031 Connexin 43 A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain. Cx43,Connexin43

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