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Article: Molecular crosstalk between insulin-like growth factors and follicle-stimulating hormone in the regulation of granulosa cell function.

Hayes, Emily / Winston, Nicola / Stocco, Carlos

2024 Volume 23, Issue 1, Page(s) e12575

Abstract: Background: The last phase of folliculogenesis is driven by follicle-stimulating hormone (FSH) and locally produced insulin-like growth factors (IGFs), both essential for forming preovulatory follicles.: Methods: This review discusses the molecular ... ...

Abstract	Background: The last phase of folliculogenesis is driven by follicle-stimulating hormone (FSH) and locally produced insulin-like growth factors (IGFs), both essential for forming preovulatory follicles. Methods: This review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral-to-preovulatory phase. Main findings: IGFs were considered co-gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function. Conclusion: FSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.
Language	English
Publishing date	2024-04-03
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2185775-1
ISSN	1447-0578 ; 1445-5781
ISSN (online)	1447-0578
ISSN	1445-5781
DOI	10.1002/rmb2.12575
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Article ; Online: Follicle-stimulating Hormone (FSH) Phosphorylation of Protein Kinase B (AKT) Remains Controversial.

Stocco, Carlos

The Journal of biological chemistry

2016 Volume 291, Issue 27, Page(s) 14385

MeSH term(s)	Follicle Stimulating Hormone/metabolism ; Granulosa Cells/metabolism ; Humans ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
Chemical Substances	Follicle Stimulating Hormone (9002-68-0) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2016-05-27
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.L116.726943
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Article: Driven Engulfment of Janus Particles by Giant Vesicles in and out of Thermal Equilibrium.

Sharma, Vaibhav / Marques, Carlos M / Stocco, Antonio

Nanomaterials (Basel, Switzerland)

2022 Volume 12, Issue 9

Abstract: The interaction between Janus colloids and giant lipid vesicles was experimentally investigated to elucidate the dynamics and mechanisms related to microparticle engulfment by lipid vesicles. Janus (Pt- ... ...

Abstract	The interaction between Janus colloids and giant lipid vesicles was experimentally investigated to elucidate the dynamics and mechanisms related to microparticle engulfment by lipid vesicles. Janus (Pt-SiO
Language	English
Publishing date	2022-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano12091434
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Article: Mechanism of negative modulation of FSH signaling by salt-inducible kinases in rat granulosa cells.

Armouti, Marah / Rodriguez-Esquivel, Miriam / Stocco, Carlos

Frontiers in endocrinology

2022 Volume 13, Page(s) 1026358

Abstract: The optimal development of preovulatory follicles needs follicle-stimulating hormone (FSH). Recent findings revealed that salt-inducible kinases (SIKs) inhibit FSH actions in humans and rodents. This report seeks to increase our understanding of the ... ...

Abstract	The optimal development of preovulatory follicles needs follicle-stimulating hormone (FSH). Recent findings revealed that salt-inducible kinases (SIKs) inhibit FSH actions in humans and rodents. This report seeks to increase our understanding of the molecular mechanisms controlled by SIKs that participate in the inhibition of FSH actions in primary rat granulosa cells (GCs). The results showed that FSH causes a transient induction of
MeSH term(s)	Animals ; Colforsin/metabolism ; Colforsin/pharmacology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Female ; Follicle Stimulating Hormone/metabolism ; Follicle Stimulating Hormone/pharmacology ; Granulosa Cells ; Humans ; Protein Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/metabolism ; Rats ; Receptors, FSH/genetics ; Receptors, FSH/metabolism ; Signal Transduction/physiology
Chemical Substances	Cyclic AMP Response Element-Binding Protein ; RNA, Messenger ; Receptors, FSH ; Colforsin (1F7A44V6OU) ; Follicle Stimulating Hormone (9002-68-0) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sik1 protein, rat (EC 2.7.11.1) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1026358
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Article ; Online: Insulin-like growth factor 1 enhances follicle-stimulating hormone-induced phosphorylation of GATA4 in rat granulosa cells.

Convissar, Scott / Bennett-Toomey, Jill / Stocco, Carlos

Molecular and cellular endocrinology

2022 Volume 559, Page(s) 111807

Abstract: Preovulatory granulosa cell (GC) differentiation is essential for the maturation and release of oocytes from the ovary. We have previously demonstrated that follicle-stimulating hormone (FSH) and insulin-like growth factors (IGFs) closely interact to ... ...

Abstract	Preovulatory granulosa cell (GC) differentiation is essential for the maturation and release of oocytes from the ovary. We have previously demonstrated that follicle-stimulating hormone (FSH) and insulin-like growth factors (IGFs) closely interact to control GC function. Similarly, we showed that GATA4 mediates FSH actions and it is required for preovulatory follicle formation. This report aimed to determine in vivo the effect of FSH on GATA4 phosphorylation and to investigate whether FSH and IGF1 interact to regulate GATA4 activity. In rat ovaries, treatment with equine chorionic gonadotropin (eCG) increased the phosphorylation of GATA4, which was confined to the nucleus of GCs. Using primary rat GCs, we observed that GATA4 phosphorylation at serine 105 increases the transcriptional activity of this transcription factor. Like FSH, IGF1 stimulated GATA4 phosphorylation at serine 105. Interestingly, GATA4 phosphorylation was significantly higher in cells cotreated with FSH and IGF1 when compared to FSH or IGF1 alone, suggesting that IGF1 augments the effects of FSH on GATA4. It was also found that the enhancing effect of IGF1 requires AKT activity and is mimicked by the inhibition of glycogen synthase kinase-3 β (GSK3β), suggesting that AKT inhibition of GSK3β may play a role in the regulation of GATA4 phosphorylation. The data support an important role of the IGF1/AKT/GSK3β signaling pathway in the regulation of GATA4 transcriptional activity and provide new insights into the mechanisms by which FSH and IGF1 regulate GC differentiation. Our findings suggest that GATA4 transcriptional activation may, at least partially, mediate AKT actions in GCs.
MeSH term(s)	Female ; Animals ; Horses ; Rats ; Follicle Stimulating Hormone/pharmacology ; Follicle Stimulating Hormone/metabolism ; Phosphorylation ; Insulin-Like Growth Factor I/pharmacology ; Insulin-Like Growth Factor I/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Cells, Cultured ; Granulosa Cells/metabolism ; Serine/metabolism ; GATA4 Transcription Factor/metabolism
Chemical Substances	Follicle Stimulating Hormone (9002-68-0) ; Insulin-Like Growth Factor I (67763-96-6) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Serine (452VLY9402) ; Gata4 protein, rat ; GATA4 Transcription Factor
Language	English
Publishing date	2022-10-21
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2022.111807
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Article ; Online: Salt-inducible kinases regulate androgen synthesis in theca cells by enhancing CREB signaling.

Rodriguez Esquivel, Miriam / Hayes, Emily / Lakomy, Oliwia / Hassan, Mariam / Foretz, Marc / Stocco, Carlos

Molecular and cellular endocrinology

2023 Volume 577, Page(s) 112030

Abstract: Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens, which play a vital role in female fertility. However, ... ...

Abstract	Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens, which play a vital role in female fertility. However, abnormally elevated androgen levels reduce fertility. Therefore, uncovering novel mechanisms regulating androgen synthesis in TCs is of great significance. We have shown that salt-inducible kinases (SIKs) regulate granulosa cell steroidogenesis. Here, we investigated whether SIKs regulate androgen production in TCs. SIK2 and SIK3 were detected in the TCs of mouse ovaries and isolated TCs. Next, TCs in culture were treated with luteinizing hormone (LH) in the presence or absence of a highly specific SIK inhibitor. SIK inhibition enhanced the stimulatory effect of LH on steroidogenic gene expression and androgen production in a concentration-dependent manner. SIK inhibition alone stimulated the expression of steroidogenic genes and increased androgen production. Activation of adenylyl cyclase with forskolin or emulation of increased intracellular cyclic AMP levels stimulated steroidogenesis, an effect that was enhanced by the inhibition of SIK activity. The stimulatory effect of downstream targets of cyclic AMP was also significantly augmented by SIK inhibition, suggesting that SIKs control targets downstream cyclic AMP. Finally, it is shown that SIK2 knockout mice have higher circulating testosterone than controls. This evidence shows that TCs express SIKs and reveal novel roles for SIKs in the regulation of TC function and androgen production. This information could contribute to uncovering therapeutic targets to treat hyperandrogenic diseases.
Language	English
Publishing date	2023-07-26
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2023.112030
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Article ; Online: Rotational and translational drags of a Janus particle close to a wall and a lipid membrane.

Sharma, Vaibhav / Fessler, Florent / Thalmann, Fabrice / Marques, Carlos M / Stocco, Antonio

Journal of colloid and interface science

2023 Volume 652, Issue Pt B, Page(s) 2159–2166

Abstract: Hypothesis: Measuring rotational and translational Brownian motion of single spherical particles reveals dissipations due to the interaction between the particle and the environment.: Experiments: In this article, we show experiments where the in- ... ...

Abstract	Hypothesis: Measuring rotational and translational Brownian motion of single spherical particles reveals dissipations due to the interaction between the particle and the environment. Experiments: In this article, we show experiments where the in-plane translational and the two rotational drag coefficients of a single spherical Brownian particle can be measured. These particle drags are functions of the particle size and of the particle-wall distance, and of the viscous dissipations at play. We measure drag coefficients for Janus particles close to a solid wall and close to a lipid bilayer membrane. Findings: For a particle close to a wall, we show that according to hydrodynamic models, particle-wall distance and particle size can be determined. For a particle partially wrapped by lipid membranes, in absence of strong binding interactions, translational and rotational drags are significantly larger than the ones of non-wrapped particles. Beside the effect of the membrane viscosity, we show that dissipations in the deformed membrane cap region strongly contribute to the drag coefficients.
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	241597-5
ISSN	1095-7103 ; 0021-9797
ISSN (online)	1095-7103
ISSN	0021-9797
DOI	10.1016/j.jcis.2023.09.026
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Article ; Online: Driven Engulfment of Janus Particles by Giant Vesicles in and out of Thermal Equilibrium

Vaibhav Sharma / Carlos M. Marques / Antonio Stocco

Nanomaterials, Vol 12, Iss 1434, p

2022 Volume 1434

Abstract	The interaction between Janus colloids and giant lipid vesicles was experimentally investigated to elucidate the dynamics and mechanisms related to microparticle engulfment by lipid vesicles. Janus (Pt–SiO 2 and Pt–MF, where MF is melamine formaldehyde) colloids do not spontaneously adhere to POPC or DOPC bilayers, but by applying external forces via centrifugation we were able to force the contact between the particles and the membranes, which may result in a partial engulfment state of the particle. Surface properties of the Janus colloids play a crucial role in the driven particle engulfment by vesicles. Engulfment of the silica and platinum regions of the Janus particles can be observed, whereas the polymer (MF) region does not show any affinity towards the lipid bilayer. By using fluorescence microscopy, we were able to monitor the particle orientation and measure the rotational dynamics of a single Janus particle engulfed by a vesicle. By adding hydrogen peroxide to the solution, particle self-propulsion was used to perform an active transport of a giant vesicle by a single active particle. Finally, we observe that partially engulfed particles experience a membrane curvature-induced force, which pushes the colloids towards the bottom where the membrane curvature is the lowest.
Keywords	Janus particles ; lipids ; vesicles ; engulfment ; adhesion ; self-propulsion ; Chemistry ; QD1-999
Subject code	620 ; 500
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: The long and short of the prolactin receptor: the corpus luteum needs them both!

Stocco, Carlos

Biology of reproduction

2012 Volume 86, Issue 3, Page(s) 85

MeSH term(s)	Animals ; Female ; Ovary/physiology ; Receptors, Prolactin/chemistry ; Receptors, Prolactin/physiology ; Signal Transduction/physiology
Chemical Substances	Receptors, Prolactin
Language	English
Publishing date	2012-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1095/biolreprod.111.098293
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Article: GATA Regulation and Function During the Ovarian Life Cycle.

Bennett-Toomey, Jill / Stocco, Carlos

Vitamins and hormones

2018 Volume 107, Page(s) 193–225

Abstract: GATA4 and GATA6 are the sole GATA factors expressed in the ovary during embryonic development and adulthood. Up today, GATA4 and GATA6 are the only transcription factors that have been conditionally deleted during ovarian development and at each major ... ...

Abstract	GATA4 and GATA6 are the sole GATA factors expressed in the ovary during embryonic development and adulthood. Up today, GATA4 and GATA6 are the only transcription factors that have been conditionally deleted during ovarian development and at each major stage of follicle maturation. The evidence from these transgenic mice revealed that GATA4 and GATA6 are crucial for follicles assembly, granulosa cell differentiation, postnatal follicle growth, and luteinization. Thus, conditional knockdown of both factors in the granulosa cells at any stage of development leads to female infertility. GATA targets impacting female reproduction include genes involved in steroidogenesis, hormone signaling, ovarian hormones, extracellular matrix organization, and apoptosis/cell division.
MeSH term(s)	Aging ; Animals ; Apoptosis ; Embryonic Development ; Extracellular Matrix/physiology ; Female ; Follicular Atresia ; GATA Transcription Factors/antagonists & inhibitors ; GATA Transcription Factors/genetics ; GATA Transcription Factors/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Luteinization ; Menstrual Cycle ; Models, Biological ; Oogenesis ; Ovary/cytology ; Ovary/embryology ; Ovary/growth & development ; Ovary/physiology ; Ovulation ; Reproduction
Chemical Substances	GATA Transcription Factors
Language	English
Publishing date	2018-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	201161-x
ISSN	2162-2620 ; 0083-6729
ISSN (online)	2162-2620
ISSN	0083-6729
DOI	10.1016/bs.vh.2018.01.014
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