Novel Signaling Pathways That Control Ovarian Follicular Development, Ovulation, and Luteinization

Js, Richards; Russell, DL; Ochsner, Scott A.; Hsieh, Minnie; Kh, Doyle; Ae, Falender; Yk, Lo; Sc, Sharma

doi:10.1210/rp.57.1.195

Cited by 365 publications

(221 citation statements)

References 133 publications

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“…More recent studies though indicate that insulin and IGFs can bind hybrid receptors of IR and IGFR monomers, resulting in greater activity spectra than previously assumed (29)(30)(31)(32). In addition to their mitogenic activities, IGFs produced in the nervous system of mammals also regulate reproduction and steroid hormone secretion (36,37), suggesting an interesting parallel with invertebrates given results of the current study. Less clear is whether mosquito and other insect ILPs have overlapping activities and how activity may be regulated when only one IR/IGFR homolog and fewer isoforms of downstream signaling components are present (8,9).…”

Section: Discussionsupporting

confidence: 54%

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Brown¹,

Clark²,

Gulia³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

226

289

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Ingestion of vertebrate blood is essential for egg maturation and transmission of disease-causing parasites by female mosquitoes. Prior studies with the yellow fever mosquito, Aedes aegypti, indicated blood feeding stimulates egg production by triggering the release of hormones from medial neurosecretory cells in the mosquito brain. The ability of bovine insulin to stimulate a similar response further suggested this trigger is an endogenous insulin-like peptide (ILP). A. aegypti encodes eight predicted ILPs. Here, we report that synthetic ILP3 dose-dependently stimulated yolk uptake by oocytes and ecdysteroid production by the ovaries at lower concentrations than bovine insulin. ILP3 also exhibited metabolic activity by elevating carbohydrate and lipid storage. Binding studies using ovary membranes indicated that ILP3 had an IC 50 value of 5.9 nM that was poorly competed by bovine insulin. Autoradiography and immunoblotting studies suggested that ILP3 binds the mosquito insulin receptor (MIR), whereas loss-of-function experiments showed that ILP3 activity requires MIR expression. Overall, our results identify ILP3 as a critical regulator of egg production by A. aegypti.

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Section: Discussionsupporting

confidence: 54%

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Brown¹,

Clark²,

Gulia³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

226

289

View full text Add to dashboard Cite

show abstract

“…Similarly, granulosa cells are epithelial-derived cells, and the adenomatosis polyposis coli (Apc) gene is known to regulate epithelial cell migration, mitosis and differentiation (McCartney & Nathke 2008). In addition, APC regulates β-catenin in the Wnt/frizzled/β-catenin signaling pathway, and this signaling pathway has been shown to be important for ovarian and follicular development (Richards et al 2002, Ricken et al 2002. Ubiquitination is also important for proper functioning of the Wnt/β-catenin/APC pathway (Voutsadakis 2008), and both Nedd4 and Ube4a are genes regulated by NT3 treatment that are involved in ubiquitination (Caren et al 2006, Gay et al 2008.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin Nt3 Promotes Ovarian Primordial to Primary Follicle Transition.

Nilsson

Dole²,

Skinner³

2009

Biology of Reproduction

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Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100-250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/ neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition.

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“…Stimulation with LH of matured preovulatory follicles induces the differentiation of granulosa cells to luteinized granulosa cells [25]. In addition, it has been demonstrated that several molecules, which are up-regulated with LH stimulation, are involved in granulosa cell differentiation and luteinization.…”

Section: Discussionmentioning

confidence: 99%

PTEN and Akt expression during growth of human ovarian follicles

Goto

Iwase

Ando

et al. 2007

J Assist Reprod Genet

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Purpose To assess the expression of PTEN and total and phosphorylated Akt in human ovarian follicles during follicular growth. Methods Immunohistochemistry of ovarian tissues and Western blotting and immunofluorescence of primary cultured luteinized granulosa cells for PTEN and Akt. Results Immunoreactivity of Akt was found in the oocytes, granulosa cells and theca cells in primordial follicles, follicles at each growing stage and luteal cells. As the follicles grew, staining for PTEN became intense in the granulosa cells, whereas the intensity of phospho-Akt became weak. Western blotting and immunofluorescence analysis using primary cultured granulosa-lutein cells showed Akt and PTEN expression, and phosphorylation of Akt in vitro. Conclusions PTEN and Akt are present in the granulosa cells during folliculogenesis. An increase in PTEN may lead to changes in proliferation and/or differentiation of granulosa cells during follicular growth via regulation of Akt phosphorylation.

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Novel Signaling Pathways That Control Ovarian Follicular Development, Ovulation, and Luteinization

Cited by 365 publications

References 133 publications

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Neurotrophin Nt3 Promotes Ovarian Primordial to Primary Follicle Transition.

PTEN and Akt expression during growth of human ovarian follicles

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