Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro

Reproductive Biology and Endocrinology

Research

Simonetta Tagliavini¹  Tommaso Trenti¹  Marco Mezzullo²  Uberto Pagotto²  Flaminia Fanelli²  Laura Riccetti³  Francesco De Pascali³  Lisa Gilioli³  Livio Casarini⁴  Lavinia Beatrice Giva⁴  Marco Marino⁴  Manuela Simoni⁵  Francesco Potì⁶ 

[1] Department of Laboratory Medicine and Pathological Anatomy, Azienda USL. NOCSAE, Via P. Giardini 1355, 41126, Modena, Italy;Endocrinology Unit, Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital. Alma Mater University of Bologna, via G. Massarenti 9, I-40138, Bologna, Italy;Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, via P. Giardini 1355, 41126, Modena, Italy;Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, via P. Giardini 1355, 41126, Modena, Italy;Center for Genomic Research, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy;Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, via P. Giardini 1355, 41126, Modena, Italy;Center for Genomic Research, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy;Department of Medicine, Endocrinology, Metabolism and Geriatrics, Azienda USL. NOCSAE, Via P. Giardini 1355, 41126, Modena, Italy;Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, via P. Giardini 1355, 41126, Modena, Italy;Center for Genomic Research, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy;Department of Neurosciences, University of Parma, via Voltuno 39/E, 43125, Parma, Italy;

关键词: LH;    hCG;    Leydig;    cAMP;    Testosterone;    Bioassay;   

DOI  :  10.1186/s12958-016-0224-3

 received in 2016-09-23, accepted in 2016-12-19,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHuman luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG.MethodsCultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated.ResultsWe found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis.ConclusionsThese data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

【 授权许可】

CC BY   
© The Author(s). 2017