Stage-Specific Responses in Gene Expression and Signaling Pathway Activation after Treatment with Prostaglandin F2 Alpha (PGF) and Interferon-Gamma (IFNG) in Bovine Corpus Luteum (CL) and Luteinizing Granulosa Cells.

In this study we examined regulation by pituitary gonadotropins of the prostaglandin F2 alpha (PGF2 alpha) receptor gene expression in the mouse ovary. Administration of pregnant mare serum gonadotropin (PMSG) to 35-day-old mice in the diestrus phase stimulated the ovary and enhanced the production of progesterone at 1 h PMSG also increased the ovarian PGF2 alpha receptor mRNA level in a time-dependent manner, reaching a sixfold maximum at 1 h. These actions of PMSG were mimicked by human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), and cholera toxin, all of which elevate intracellular adenosine 3',5'-cyclic monophosphate (cAMP). In situ hybridization revealed that PGF2 alpha receptor mRNA was localized to the corpus luteum, but the intensity of staining varied among corpora lutea in the same ovary. Exogenous PGF2 alpha inhibited the PMSG-stimulated progesterone production. These results demonstrate that gonadotropins may induce the expression of the PGF2 alpha receptor gene in luteal cells of the corpus luteum, probably by acting through a cAMP-mediated pathway, and that expression of the PGF2 alpha receptor may be functionally associated with the decrease in serum progesterone level.

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Identification of optimal housekeeping genes for examination of gene expression in bovine corpus luteum

Reproductive Biology ◽

10.1016/j.repbio.2012.10.010 ◽

2012 ◽

Vol 12 (4) ◽

pp. 362-367 ◽

Cited By ~ 25

Author(s):

Robert Rekawiecki ◽

Joanna Rutkowska ◽

Jan Kotwica

Keyword(s):

Gene Expression ◽

Corpus Luteum ◽

Housekeeping Genes ◽

Bovine Corpus Luteum

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Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway

Cell Death Discovery ◽

10.1038/s41420-020-00324-9 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Gamze Bildik ◽

Nazli Akin ◽

Yashar Esmaeilian ◽

Francesko Hela ◽

Ceren Sultan Yildiz ◽

...

Keyword(s):

Corpus Luteum ◽

Signaling Pathway ◽

Granulosa Cells ◽

Molecular Mechanisms ◽

Terminal Differentiation ◽

Reproductive Technologies ◽

Activin A ◽

Jnk Pathway ◽

Jnk Signaling ◽

Jnk Signaling Pathway

Abstract Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.

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