Protein kinases and ovarian functions

Sirotkin, Alexander V.; Makarevich, Alexander V.; Grosmann, Roland

doi:10.1002/jcp.22364

Cited by 12 publications

(8 citation statements)

References 79 publications

(247 reference statements)

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“…This observation is in agreement with previous reports on stimulating (CHEADLE et al 2008;VIEGAS et al 2008;SIROTKIN et al 2010b) but not on inhibiting (PELUSO et al 1993;GRAWES & LAWRENCE 1996;HSUEH et al 1996;HILLIER & TETSUKA 1997) action of cAMP/PKA on proliferation of ovarian cells in other species. These observations are in line with previous reports on involvement of cAMP-dependent intracellular mechanisms in up-regulation of ovarian follicular growth in rat (MCKENNA et al 2005) and rabbit (SIROTKIN et al 2008a;CHRENEK et al 2012;SIROTKIN et al 2010c). Nevertheless, this is the first evidence that cAMP-induced rabbit ovarian follicular growth can be due to promotion of cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…This is the first data on the action of dbcAMP on rabbit ovarian apoptosis. Our observations correspond to the increase in morphological signs of atresia observed in rabbit ovaries after administration of PDE inhibitor (SIROTKIN et al 2010c) or dbcAMP (CHRENEK et al 2012). The dbcAMP-induced accumulation of both proliferation-and apoptosis-related substances suggest that dbcAMP administration can promote cellular turnover (replacement) in rabbit ovaries.…”

Section: Discussionsupporting

confidence: 85%

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The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

Sirotkin¹,

Baláži²,

Chrenek³

2014

folia biol (krakow)

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SIROTKIN A. V., BALAZI A., CHRENEK P. 2014. The cAMP analogue, dbcAMP, affects rabbit ovarian cell proliferation, apoptosis, release of steroids and response to hormones. Folia Biologica (Kraków) 62: 211-218.Cyclic adenosine monophosphate (cAMP)-related intracellular mechanisms can be important in the control of reproductive processes. The aim of the present study was to examine possible hormonal and intracellular mechanisms mediating the action of cAMP on ovarian cell functions, in particular the mechanisms of stimulatory action of dbcAMP on rabx and caspase 3), plasma level of progesterone and estradiol, and release of progesterone, testosterone and estradiol by isolated ovarian fragments, as well as the response of these fragments to hormonal regulators of ovarian steroidogenesis -FSH, IGF-I and ghrelin (all at doses of 100 ng/ml). Release of hormones was assessed by RIA. The expression of markers of proliferation and apoptosis was evaluated by electrophoresis-Western blotting. Administration of dbcAMP resulted in a reduction of the estradiol level, but not progesterone level in rabbit plasma, as well as in progesterone and estradiol release, but not testosterone release, by isolated ovarian fragments. Additions of FSH, IGF-I and ghrelin to culture medium reduced the release of progesterone and increased testosterone and estradiol output by fragments isolated from control animals. The release of all these hormones was increased by fragments isolated from dbcAMP-treated animals. Both dbcAMP injections and addition of FSH, IGF-I and ghrelin to culture medium promoted the accumulation of proliferation and apoptosis markers in cultured ovarian fragments, whilst dbcAMP increased the stimulatory effects of hormones on these markers. The present observations (1) confirm involvement of peptide hormones FSH, IGF-I and ghrelin in the control of ovarian cell proliferation, apoptosis and steroid hormone release; (2) demonstrate the involvement of cAMP-dependent intracellular mechanisms in promotion of rabbit ovarian cell proliferation, apoptosis and in regulation of ovarian steroidogenesis; (3) suggest the involvement of cAMP-dependent mechanisms in mediating and/or promoting the effect of peptide hormones FSH, IGF-I and ghrelin on ovarian cell proliferation, apoptosis, but not on steroidogenesis; (4) suggest that the stimulatory action of dbcAMP on rabbit reproduction could be due to dbcAMP-induced changes in ovarian cell proliferation, apoptosis, steroid hormone release and the response of these processes to hormonal regulators.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 85%

The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

Sirotkin¹,

Baláži²,

Chrenek³

2014

folia biol (krakow)

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“…Both cAMP [1][2][3][4][5] and cGMP [6,7] play an important role in the control of ovarian cell proliferation, apoptosis, secretory activity, and oocyte maturation and in mediating the effect of hormonal stimulators on these processes. cAMP can mediate the effect of some hormones on oviduct functions too [8][9][10]. Both cyclic nucleotides are hydrolyzed by the enzymes known as phosphodiesterases (PDEs).…”

Section: Introductionmentioning

confidence: 99%

Activators of protein kinase A and oxytocin affect rabbit reproduction

Baláži¹,

Sirotkin²,

Chrenek³

2012

Open Life Sciences

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The aim of this study was to examine the effect of activators of protein kinase A — 3-isobutyl-1-methyl-xanthine (IBMX) and dibutyryl cyclic adenosine monophosphate (dbcAMP) — and of oxytocin (OT) on rabbit female reproductive function. We used equine chorionic gonadotropin (eCG) to improve follicular development and rabbit estrous synchronization and human chorionic gonadotropin (hCG) to induce ovulation. In the experimental group, the females were stimulated using gonadotropins together with either IBMX, dbcAMP or OT. In the animals kept until parturition, the conception rate, parturition rate, and numbers of stillborn and weaned pups were recorded. In the animals euthanized 18–19 hours after insemination, the eggs were flushed from the oviducts and cultured up to the blastocyst cell stage. Numbers of corpora lutea, zygotes, morulas and blastocysts were determined. Both dbcAMP and OT, but not IBMX, decreased conception and parturition rate. Both IBMX and OT, but not dbcAMP, decreased pup mortality rate. All three tested substances increased the weaning rate. Both IBMX and dbcAMP, but not OT, increased the numbers of corpora lutea, zygotes, and embryos at morula and hatching blastocyst stages. These observations confirm the stimulatory role of the protein kinase A-dependent signaling pathway activated by IBMX and dbcAMP in rabbit reproduction. OT may decrease pups mortality.

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“…cell proliferation and apoptosis, oocyte maturation, hormone release and response to hormones, and mediating the action of hormones on ovarian functions (7). As TKIs target protein kinase receptors in tumor cells and inhibit their phosphorylation, we speculate that TKIs can also interact with protein kinases in the ovary and influence ovarian function and reproductive potential.…”

Section: Lapatinib-induced Inhibition Of Ovarian Function Is Counteramentioning

confidence: 92%

Lapatinib‑induced inhibition of ovarian function is counteracted by the STAT3 pathway both in vivo and in vitro

Liao

Xue

et al. 2020

Oncol Rep

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The present study was designed to ascertain whether lapatinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), affects ovarian reserve and fertility potential in a mouse model. Female C57BL/6 mice were treated with either vehicle or lapatinib (100 or 200 mg/kg/day orally) for 4 weeks, after which body weight, vaginal smears, follicle numbers, serum anti-Müllerian hormone (AMH) levels and mating outcomes were analyzed to assess the ovarian reserve and reproductive function. Slices from the ovaries of 4-week-old mice were cultured with lapatinib (0, 5 or 10 µM) for 24 and 48 h, and protein expression levels were assessed to validate the changes in signaling pathways. The results indicated that mice treated with 200 mg/kg lapatinib showed a slight decrease in body weight compared to those treated with vehicle or 100 mg/kg lapatinib. There was no statistical difference in estrous cyclicity among the three groups. No significant difference was observed in follicle numbers, AMH levels, histological morphologies of the ovaries or mating outcomes in the three groups of mice. Western blotting and immunohistochemical staining of the EGF receptor and its main downstream signaling pathways showed decreased phosphorylation of EGFR and mitogen-activated protein kinase (MAPK)3/1 and increased phosphorylation of signal transducers and activators of transcription (STAT)3 in the lapatinib-treated groups compared to the control group. Our study suggests that lapatinib has little effect on ovarian reserve and reproductive function in a mouse model. This lack of effect of lapatinib on ovarian function may be due to the activation of the STAT3 signaling pathway that counteracts the inhibitory effects of lapatinib on EGF receptors.

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Protein kinases and ovarian functions

Cited by 12 publications

References 79 publications

The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

Activators of protein kinase A and oxytocin affect rabbit reproduction

Lapatinib‑induced inhibition of ovarian function is counteracted by the STAT3 pathway both in vivo and in vitro

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