[PDF] FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH. | Semantic Scholar (2024)

A novel model is proposed in which FSH downregulates FoxO1-dependent apoptosis in MGCs by coordinating the PKA–PI3K–AKT–FoxO1 axis and FoxO’s positive feedback.

FoxO3 is expressed in chicken reproductive tissues, including follicles and ovarian granulosa cells, and promotes apoptosis of chicken ovarian granULosa cells.

Results provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of FOXL2 and GATA4, and tumor formation.

The results suggest that the regulation and/or function of FOXO3 in the primate primordial follicle may differ than that of the rodent, and AKT/p-AKT is expressed in macaque primordial oocytes, suggesting that similar upstream events but different downstream effects may regulate primordial hair follicle activation in nonhuman primates compared to rodents.

It is suggested that FoxO1 is regulated by the GnRH signaling pathway and functions as a negative regulator of FSHβ gene expression.

It is found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FoxO1 relocation from the nucleus to the cytoplasm.

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Affymetrix microarray and database analyses identified, and real time RT-PCR verified, that genes within the lipid, sterol, and steroidogenic biosynthetic pathways (Hmgcs1, Hmgcr, Mvk, Sqle, Lss, Cyp51, Tm7sf2, Dhcr24 and Star, Cyp11a1, and Cyp19), including two key transcriptional regulators Srebf1 and SreBF2 of cholesterol bios

It is demonstrated that FOXO1 phosphorylation and cellular localization is regulated by insulin signaling in gonadotropes and thatFOXO1 inhibits Lhb transcription, which suggests that FoxO1 may play an important role in controlling LH levels in response to metabolic cues.

The present study utilized immunohistochemical analysis to determine the ovarian localization and regulation of FoxO1 protein levels in neonatal rats, immature rats during gonadotropin-induced follicular development, ovulation, and luteinization, and in spontaneously developing ovarian cysts of aging rats, suggesting roles in these physiological processes.

The results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3.

Follicles of FSHβ knockout mice develop a well organized thecal layer, which is positive for P450 17α-hydroxylase and LH receptor messenger RNAs (mRNAs), which indicates that theca recruitment is completed autonomously with respect to FSH.

The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development, and may give some insight into oocyte-borne genetic aberrations that cause defects in folliculardevelopment and anovulation in human diseases, such as premature ovarian failure.

The elevated expression of FKHR in granulosa cells of growing follicles indicates that FK HR may be linked to the proliferation of granul Rosa cells and that its phosphorylation by FSH, IGF-I, and other factors may impact its functional activity in this process.

IGF-I and FSHR are selectively coexpressed in healthy, growing murine follicles and that FSH does not affect IGF-I expression but that IGF- I augments granulosa cell F SHR expression, suggesting that ovarian IGF-i expression serves to enhance granul Rosa cell FSH responsiveness by augmenting FSHr expression.

A FoxO–Smad synexpression group or group of genes that are jointly induced by a common mechanism in response to TGF-β is defined, suggesting that stress reactions and adaptive functions accompany the cytostatic response of keratinocytes to T GF-β.

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