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Endocrine Abstracts (2016) 41 GP186 | DOI: 10.1530/endoabs.41.GP186

ECE2016 Guided Posters Reproduction & Endocrine Disruption (10 abstracts)

FSH increases the different LH- and hCG-dependent intracellular signalling and the downstream life/death signals in vitro

Livio Casarini 1, , Laura Riccetti 1 , Francesco De Pascali 1 , Alessia Nicoli 3 , Simonetta Tagliavini 4 , Tommaso Trenti 4 , Giovanni Battista La Sala 3, & Manuela Simoni 1,

1Unit of Endocrinology, Department Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Center for the Genomic Research, University of Modena and Reggio Emilia, Modena, Italy; 3Unit of Obstetrics and Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 4Department of Clinical Pathology, Azienda USL, Modena, Italy; 5Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Background: Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy. They were routinely used in assisted reproduction techniques (ART) assuming they are equivalent, due to their binding to a common receptor (LHCGR). However, differences between LH and hCG were demonstrated at molecular and physiological level.

Aim: The aim of this study is to evaluate how follicle-stimulating hormone (FSH) co-treatment, in the ART therapeutic dose-range, affects the different LH- and hCG-specific responses in vitro.

Methods: We evaluated phospho-CREB, -ERK1/2 and -AKT activation by Western blotting, gene expression by real-time PCR, cAMP, progesterone and estradiol production by ELISA, and cell viability by MTT assay in human granulosa-lutein cells (hGLC). LH and hCG dose-response experiments (0.1 pM–1.0 nM range) were performed, in the presence of 10 nM FSH.

Results: In the presence of FSH, hCG biopotency is about 5-fold increased, in cAMP activation. Moreover, different LH and hCG dose-response curves were observed, in terms of 50% effective doses (EC50s), hill-slopes and maximal levels (Mann–Whitney’s U-test; P<0.05; n=6), suggesting hormone-specific receptor cooperativity and biopotency. Accordingly, the cAMP-dependent CREB phosphorylation and steroid production increased under hCG and FSH co-treatment. Surprisingly, the activation of the steroidogenic cAMP/PKA/CREB signalling cascade did not change upon LH treatment, in the presence of FSH. However, FSH increased the LH-dependent ERK1/2 and AKT phosphorylation, the expression of the X-linked inhibitor of apoptosis (XIAP) gene, and the cell viability (Mann–Whitney’s U-test; P<0.05; n=4), resulting in anti-apoptotic effects.

Conclusions: FSH potentiates the LH-dependent anti-apoptotic and the hCG steroidogenic (and pro-apoptotic) potential in vitro. The different modulatory activity of FSH on LH and hCG action in vitro reflects their different physiological functions, consisting in proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy.

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