Resistin decreases insulin-like growth factor I-induced steroid production and insulin-like growth factor I receptor signaling in human granulosa cells - Archive ouverte HAL
Article Dans Une Revue Fertility and Sterility Année : 2013

Resistin decreases insulin-like growth factor I-induced steroid production and insulin-like growth factor I receptor signaling in human granulosa cells

Résumé

OBJECTIVE: To identify resistin in human ovarian follicles and investigate the effect and the molecular mechanisms associated with resistin on steroidogenesis in human granulosa cells (GCs). DESIGN: The effects of recombinant human resistin on the secretion of progesterone (P) and estradiol (E2) by cultured human GCs were investigated. SETTING: Academic institutions. PATIENT(S): Twenty infertile and healthy women undergoing IVF. INTERVENTION(S): Primary human GC cultures stimulated with recombinant human resistin (10 ng/mL). MAIN OUTCOME MEASURE(S): Determination of messenger RNA (mRNA) and protein expression of resistin in fresh human GCs by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblot and immunohistochemistry, respectively; measurement of P and E2 levels in the conditioned media by radioimmunoassay; determination of cell proliferation by tritiated thymidine incorporation; and analysis of signaling pathways activation by immunoblot analysis. RESULT(S): Human GCs and theca cells express resistin. In primary human GCs, resistin decreases P and E2 secretion in response to insulin-like growth factor I (IGF-I). This was associated with a reduction in the P450 aromatase and P450scc (cholesterol side-chain cleavage cytochromes P450) (P450scc) protein levels but not those of 3β-hydroxysteroid dehydrogenase (3β-HSD) or steroidogenic acute regulatory protein (StAR) and with a decrease in IGF-I-induced IGF-I receptor and mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Resistin treatment does not affect IGF-I-induced cell proliferation and basal steroidogenesis (there is no IGF-I or follicle-stimulating hormone stimulation). In the basal state, resistin rapidly stimulates Akt and MAPK ERK1/2 and p38 phosphorylation in primary human GCs. CONCLUSION(S): Resistin is present in human GCs and theca cells. It decreases P and E2 secretion, P450scc and P450 aromatase protein levels, and IGF-IR signaling in response to IGF-I in primary human GCs.

Domaines

Autre [q-bio.OT]

Dates et versions

hal-01129712 , version 1 (10-03-2015)

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Maxime Reverchon, Marion Cornuau, Christelle Rame, Fabrice Guerif, Dominique Royère, et al.. Resistin decreases insulin-like growth factor I-induced steroid production and insulin-like growth factor I receptor signaling in human granulosa cells. Fertility and Sterility, 2013, 100 (1), pp.247-255. ⟨10.1016/j.fertnstert.2013.03.008⟩. ⟨hal-01129712⟩
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