Granulosa Cell-Specific Androgen Receptors Are Critical Regulators of Ovarian Development and Function.

Sen, Aritro; Hammes, Stephen R.

doi:10.1093/biolreprod/83.s1.163

Cited by 43 publications

(82 citation statements)

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“…As the animals aged, however, the ability of exogenous gonadotropins to override this defect was lost, and reduced oocyte numbers were observed from natural mating and superovulation paradigms. 692 Failure of the ovary to respond to exogenous gonadotropins concurrent with a reduction in the total number of offspring born over a long-term fertility study (19 in KO versus 119 in WT mice) supports the POF phenotype observed in the global AR-knockout models. 183,185,290 The GCARcKO presented by Sen and Hammes was made using the Amhr2-cre mouse, which has been found to be active in tissues other than granulosa cells including the pituitary, 696 which may complicate the findings.…”

Section: Mice With Ovarian-specific Deletion Of Armentioning

confidence: 67%

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Steroid Receptors in the Uterus and Ovary

Binder

Winuthayanon

Hewitt

et al. 2015

Knobil and Neill's Physiology of Reproduction

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Section: Mice With Ovarian-specific Deletion Of Armentioning

confidence: 67%

“…To circumvent this, two conditional knockout mouse models have been developed to remove AR specifically in granulosa cells of the ovary. 691,692 These models provide a unique way to explore the role(s) of AR in female fertility and ovarian function.…”

Section: Mice With Ovarian-specific Deletion Of Armentioning

confidence: 99%

Steroid Receptors in the Uterus and Ovary

Binder

Winuthayanon

Hewitt

et al. 2015

Knobil and Neill's Physiology of Reproduction

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“…Activation of the PR can be seen as both anti-and pro-proliferative in uterus and breast respectively. In addition, the pattern of response will be determined by the PR isoform expressed [84]. At this stage we have not established whether the PR in GCT is PRA, PRB, or both.…”

Section: Progesterone Receptormentioning

confidence: 99%

“…Female mice null for the AR have subfertility secondary to increased GC apoptosis in the pre-ovulatory follilcles [83]. Sen and Hammes [84] have recently demonstrated that GC-specific AR gene deletion largely phenocopies the global knockout mice indicating that the reproductive phenotype reflects the role of the AR in GC. The AR appears to play a fundamental role in GC growth and in preventing follicular atresia [84].…”

Section: Androgen Receptormentioning

confidence: 99%

“…Sen and Hammes [84] have recently demonstrated that GC-specific AR gene deletion largely phenocopies the global knockout mice indicating that the reproductive phenotype reflects the role of the AR in GC. The AR appears to play a fundamental role in GC growth and in preventing follicular atresia [84]. Activating and inactivating mutations of the AR are features of prostate and breast cancer respectively; mutations in the AR have not been systematically sought in GCT.…”

Section: Androgen Receptormentioning

confidence: 99%

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Nuclear Receptor Profiling of Ovarian Granulosa Cell Tumors

Alexiadis¹,

Eriksson

Jamieson

et al. 2011

HORM CANC

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Granulosa cell tumors of the ovary (GCT) represent ~5% of malignant ovarian tumors. The adult form is defined by a mutation in the FOXL2 gene. GCT exhibit many of the features of normal proliferating granulosa cells. We have profiled the expression of the 48 human nuclear receptors (NR) by quantitative RT-PCR in a panel of GCT and in two GCT-derived cell lines, COV434 and KGN. The highest level of expression is seen for COUP-TF2 with abundant expression of PPARγ, SF-1, and TR-α. Estrogen receptor (ER)-β is the most abundant of the steroid receptors with relatively high expression also of AR, ER-α, and PR. The concordance of expression for each NR across the tumors is remarkably high with same discordance between the cell lines and the tumors, particularly the COV434 line. No significant differences were observed with respect to tumor stage for NR expression. These findings provide a full profile of NR expression in GCT which will enable full characterization of their roles and potential as therapeutic targets.

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Suppressor of cytokine signaling 4 (SOCS4): Moderator of ovarian primordial follicle activation

Sutherland¹,

Keightley²,

Nixon³

et al. 2011

Journal Cellular Physiology

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Mammalian ovarian primordial follicle activation and regulation is considered as one of the most important stages of folliculogenesis and as such requires exquisite control. Selection of quiescent follicles to enter the growing pool determines the rate of supply of maturing follicles over the female reproductive lifespan. To coordinate this process a range of positive and negative input signals contribute to determine follicle fate. This study demonstrates that the cytokine Leukemia Inhibitory Factor (LIF) activates the Janus Kinase 1/Signal Transducers and Activators of Transcription 3 (JAK1/STAT3) signaling pathway in pre-granulosa cells and positively regulates primordial follicle activation. Negative regulation of the JAK/STAT pathway is controlled by the suppressor of cytokine signaling 4 (SOCS4) protein, which target members of negative feedback loops, Cardiotrophin like Cytokine (CLC), Poly (rC) Binding Protein 1 (PCBP1), and Cytosolic Malate Dehydrogenase (MDH1) to suppress follicle growth and development.

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Granulosa Cell-Specific Androgen Receptors Are Critical Regulators of Ovarian Development and Function.

Cited by 43 publications

References 0 publications

Steroid Receptors in the Uterus and Ovary

Steroid Receptors in the Uterus and Ovary

Nuclear Receptor Profiling of Ovarian Granulosa Cell Tumors

Suppressor of cytokine signaling 4 (SOCS4): Moderator of ovarian primordial follicle activation

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