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Comment |
Sharma,S.C. and Richards,J.S. reported the regulation of AP1 (Jun/Fos) Factor expression and activation in
ovarian granulosa cells: Relation of JunD and Fra2 to terminal
differentiation.
The expression patterns of Jun and Fos family members
in response to hormones (follicle-stimulating hormone (FSH), luteinizing hormone
(LH), and cAMP) were distinct. JunB, c-Jun, c-Fos, and Fra2 were rapidly but
transiently induced by FSH in immature granulosa cells. JunD and Fra2 were induced
by LH and maintained as granulosa cells terminally differentiated into luteal cells.
Forskolin and phorbol myristate acetate acted synergistically to enhance transcription
of an AP1(-73COL)-luciferase construct. JunD appears to be one mediator of this
effect, since JunD was a major component of the AP1-DNA binding complex in
granulosa cells, and menin, a selective inhibitor of JunD, blocked transcription of
-73COL-luciferase. Thus, FSH and LH via cAMP induce specific AP1 factors, the
AP1 expression patterns are distinct, and that of JunD and Fra2 correlates with the
transition of proliferating granulosa cells to terminally differentiated, non-dividing luteal
cells.
Stocco CO, et al reported a calcium/calmodulin-dependent activation of ERK1/2 mediates
JunD phosphorylation and induction of nur77 and 20 alpha-hsd
genes by prostaglandin F-2 alpha in ovarian cells.
In
luteinized granulosa cells, PGF(2alpha) stimulates in vitro nur77
expression in a time- and dose-dependent manner. Serial 5'-deletion of the
nur77 promoter revealed that the necessary and sufficient elements for
PGF(2alpha) induction of Nur77 promoter activity are located between the
nueleotides -86 and -33 upstream of the transcription start site, this region
containing two AP1 elements. JunD binds to these A-PI sites, but its binding
is not stimulated by PGF(2alpha). However, mutation of the AP1 sites as well
as a dominant-negative JunD abolished nur77 induction by PGF(2alpha).
PGF(2alpha) induces phosphorylation of JunD bound to the nur77 promoter.
Stimulation of nur77 expression and JunD phosphorylation were prevented by
inhibitors of calcium, calmodulin, or ERK1/2 kinase. PGF2,induced ERK1/2
phosphorylation was prevented by calcium/calmodulin inhibitors. It was concluded
that activation of JunD through a calmodulim-dependent activation of ERKI/2
mediates nur77 induction by PGF2,.
Immunohistochemical Analysis of Tyrosine Phosphorylation and AP-1 Transcription Factors c-Jun, Jun D, and Fos Family During Early Ovarian Follicle Development in the Mouse Oktay KH, et al .
The growth control mechanism of early-stage ovarian follicles is unknown. Tyrosine phosphorylation of signaling molecules and changes in expression and activation of AP-1 transcription factors have been implicated in growth regulation of numerous cell types. In this study, we used immunohistochemistry to analyze tyrosine phosphorylation patterns and expression and activation of selected AP-1 transcription factors in mouse ovarian follicles. The ovaries were collected from B62F1/J mice in estrus. Representative sections were immunostained for phosphotyrosine, phospho-c-Jun, Jun D, and c-Fos. Phosphotyrosine staining was perioocytic from the transitional stage until approximately 5 to 7 layers of granulosa cells had formed. Perioocytic staining was then replaced by scattered stippled staining in granulosa cells of larger follicles. Phospho c-Jun was exclusively expressed in mitotic granulosa cells of follicles from transitional to antral stages. Jun D was expressed in the oocytes of primordial, primary, or transitional follicles and disappeared at the 2-layer preantral stage. Fos was present in corpora lutea and theca cells but not in granulosa cells. Collectively, these data indicate that phosphotyrosine signaling and AP-1 transcription factors are intimately involved in early stages of ovarian follicle growth.
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