Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro. (15th February 2016)

• Record Type: Journal Article
• Authors: Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Nicoli, Alessia; Tagliavini, Simonetta; Trenti, Tommaso; La Sala, Giovanni Battista; Simoni, Manuela
• Is Part Of: Molecular and cellular endocrinology. Volume 422(2016)
• Page Start: 103
• Page End: 114
• Publication Date: 2016-02-15
• Subjects: FSH -- LH -- hCG -- LHCGR -- Granulosa cells; FSH follicle-stimulating hormone -- LH luteinizing hormone -- hCG human chorionic gonadotropin -- TSH thyroid-stimulating hormone -- FSHR FSH receptor -- LHCGR LH and hCG receptor -- GPCRs G protein-coupled receptors -- PKA protein kinase A -- CREB cAMP-responsive element binding protein -- ERK1/2 extracellular-regulated kinase -- PI3K phosphatidylinositol-3-kinases -- AKT protein kinase B -- ART assisted reproduction techniques -- hGLC human granulosa-lutein cells -- HRM High Resolution Melting -- IBMX 3-isobutyl-1-methylxanthine -- androstenedione 4-androstene-3, 17-dione -- RPS7 ribosomal subunit protein 7 -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- SD standard deviation -- EC20 20% maximal effective dose -- EC50 half maximal effective dose -- H-slope hill slope value -- EGF epidermal growth factor -- AREG amphiregulin gene -- EREG epiregulin gene -- CASP3 procaspase 3 gene -- TP53 p53 gene -- XIAP X-linked inhibitor of apoptosis factor gene -- STARD1 steroidogenesis-related StAR gene -- CYP19A1 aromatase gene -- Tβ-RII transforming growth factor β receptor; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.12.008
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecular and physiological level. In this study, we demonstrated for the first time that co-treatment with a follicle-stimulating hormone (FSH) dose in the ART therapeutic range potentiates different LH- and hCG-dependent responses in vitro, measured in terms of cAMP, phospho-CREB, -ERK1/2 and -AKT activation, gene expression, progesterone and estradiol production in human granulosa-lutein cells (hGLC). We show that in the presence of FSH, hCG biopotency is about 5-fold increased, in the presence of FSH, in terms of cAMP activation. Accordingly, CREB phosphorylation and steroid production is increased under hCG and FSH co-treatment. LH effects, evaluated as steroidogenic cAMP/PKA pathway activation, do not change in the presence of FSH, which, however, increases LH-dependent ERK1/2 and AKT, but not CREB phosphorylation, resulting in anti-apoptotic effects. The different modulatory activity of FSH on LH and hCG action in vitro corresponds to their different physiological functions, reflecting proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy from the luteal phase onwards. Highlights: FSH potentiates the different response to LH and hCG in granulosa cells, in vitro . LH treatment of granulosa cells results mainly in anti-apoptotic effects. hCG treatment of granulosa cells results mainly in steroidogenic effects.