Different levels of leptin regulate different target enzymes involved in progesterone synthesis

Bilbao, María Guillermina; Yorio, María Paula Di; Faletti, A.

doi:10.1016/j.fertnstert.2012.12.014

Cited by 17 publications

(5 citation statements)

References 42 publications

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“…In the mentioned study, in vitro leptin treatment with low dose (10 ng/mL) increased P 4 accumulation by luteinized granulosa cells, whereas the high dose (1000 ng/mL) had an inhibitory effect. In a more recent study in rat ovary, the in vivo administration of different LEP doses activated distinctive steroidogenic enzymes, with particular emphasis for 3-beta-hydroxysteroid dehydrogenase (3 β HSD) modulation, in a dose-dependent manner [44]. In our model, we could also see that early CL LEP treatment in a lower dose (5 ng/mL) increased P 4 secretion, while the higher dose (200 ng/mL) caused no effect.…”

Section: Discussionmentioning

confidence: 50%

Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: AnIn VitroStudy

Galvão

Tramontano

Rebordão

et al. 2014

Mediators of Inflammation

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Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2α, nitric oxide (nitrite), tumor necrosis factor-α (TNF); macrophage migration inhibitory factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in equine corpus luteum (CL) from early and mid-luteal stages. LEPR expression was decreased in late CL, while GHR/Ghr-R1A system was increased in the same stage. Regarding secretory activity, GHR decreased P4 in early CL, but increased PGF2α, nitrite and TNF in mid CL. Conversely, LEP increased P4, PGE2, angiogenic activity, MIF, TNF and nitrite during early CL, in a dose-dependent manner. The in vitro effect of LEP on secretory activity was reverted by GHR, when both factors acted together. The present results evidence the presence of LEP and GHR systems in the equine CL. Moreover, we suggest that LEP and GHR play opposing roles in equine CL regulation, with LEP supporting luteal establishment and GHR promoting luteal regression. Finally, a dose-dependent luteotrophic effect of LEP was demonstrated.

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Section: Discussionmentioning

confidence: 50%

Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: AnIn VitroStudy

Galvão

Tramontano

Rebordão

et al. 2014

Mediators of Inflammation

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“…Together, these data suggest that insulin and/or leptin contribute to the altered steroid synthesis of B6‐HFD and LY females. Indeed, stimulation of whole ovary tissue, microdissected follicles, or isolated granulosa cells with leptin or insulin has been correlated with increased expression of Star , Cyp11a1 , and/or Hsd3b (Poretsky et al, ; Sekar et al, ; Ruiz‐Cortes et al, ; Swain et al, ; Bilbao et al, ).…”

Section: Discussionmentioning

confidence: 99%

Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of mRNAs stored in the ovulated oocyte

Pohlmeier

Xie

Kurz

et al. 2014

Molecular Reproduction Devel

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Obese women who are able to attain pregnancy are at increased risk for early-pregnancy loss due, in part, to reduced oocyte quality. We and others have demonstrated that female Lethal Yellow (LY) mice and female C57BL/6 mice fed a high fat diet (B6-HFD) exhibit phenotypes consistent with human obesity. These studies also showed that zygotes collected from LY and B6-HFD females have reduced developmental competence. The current hypothesis is that LY and B6-HFD females exhibit an abnormal response to gonadotropin stimulation compared to C57BL/6 controls fed normal rodent chow (B6-ND), resulting in the ovulation of oocytes with an altered molecular phenotype which may contribute to its reduced developmental competence. To test this hypothesis, age-matched B6-ND, B6-HFD, and LY females were stimulated with exogenous gonadotropins, then circulating hormone levels and the phenotypes of ovulated oocytes were analyzed. There was no difference in ovulation rate or in the percentage of morphologically abnormal oocytes collected from the oviduct of any females. Progesterone and progesterone/estradiol ratios, however, were increased in B6-HFD and LY compared to B6-ND females 16 hr post-human chorionic gonadotropin treatment. The transcript abundance of several candidate oocyte genes was also increased in B6-HFD- and LY-derived oocytes compared to B6-ND-derived oocytes. These data suggest that increased insulin and leptin levels of obese females elevated circulating progesterone concentrations, altered transcriptional activity during oocyte growth, and/or impaired mechanisms of RNA translation and degradation during oocyte maturation. These changes in mRNA abundance likely contribute to reduced oocyte quality and the subsequent poor embryogenesis associated with obesity.

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“…In porcine granulosa cells, IGF1 induction of cholesterol side-chain cleavage cytochrome (P450scc) expression is directly and specifically mediated through ERK phosphorylation (Denner et al 2010). Recently, we observed a significant decrease in the ovarian expression of P450scc in parallel with that of ERK1/2 phosphorylation in the same samples of ovarian tissue from rats that received the acute treatment for the present work (Bilbao et al 2013). This result is consistent with the finding that PD 98059, a specific inhibitor of ERK1/2 activation, was able to reverse the action of leptin on progesterone secretion in our in vitro studies.…”

Section: Signalling Pathways Regulated By Leptinmentioning

confidence: 51%

Ovarian signalling pathways regulated by leptin during the ovulatory process

et al. 2013

Self Cite

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Leptin, a protein secreted by different tissues, is able to exert both stimulatory and inhibitory effects on the ovulatory process. Thus, we investigated whether these opposite effects involve changes in the ovarian signalling pathways in response to different levels of leptin. To this end, we performed both in vivo and in vitro assays using immature rats primed with gonadotrophins to induce ovulation. The acute treatment with leptin, which inhibits the ovulatory process, caused a significant decrease in the phosphorylation of both STAT3 and ERK1/2 and a simultaneous increase in suppressors of cytokine signalling 3 (SOCS3) protein. However, daily administration of a low dose of leptin, which induces the ovulatory process, showed increased phosphorylation of both STAT3 and ERK1/2 and a decreased expression of SOCS3 protein. Using ovarian explant cultures, we also found that leptin was able to activate both STAT3 and ERK1/2 at 10 ng/ml but only STAT3 at 300-500 ng/ml. In addition, at 100-300 ng/ml, leptin increased protein but not mRNA expression of SOCS3. The addition of specific inhibitors of JAK/STAT and MAPK signalling pathways suppressed both the increase and the decrease in leptin-induced progesterone secretion. These results indicate that i) different levels of leptin are able to regulate STAT3, ERK1/2 and SOCS3 at both intra-and extra-ovarian level and that ii) the dual action of leptin on steroidogenesis seems to occur, at least in part, through both the ERK and STAT cascades.

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Different levels of leptin regulate different target enzymes involved in progesterone synthesis

Cited by 17 publications

References 42 publications

Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: AnIn VitroStudy

Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: AnIn VitroStudy

Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of mRNAs stored in the ovulated oocyte

Ovarian signalling pathways regulated by leptin during the ovulatory process

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