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Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro
- Source :
- Reproductive Biology and Endocrinology : RB&E
- Publication Year :
- 2016
-
Abstract
- Background Human 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. Methods Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. Results We 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. Conclusions These 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. Electronic supplementary material The online version of this article (doi:10.1186/s12958-016-0224-3) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
LH
medicine.medical_specialty
Cell signaling
endocrine system
medicine.drug_class
Leydig
hCG
030209 endocrinology & metabolism
Chorionic Gonadotropin
03 medical and health sciences
Mice
0302 clinical medicine
Endocrinology
Internal medicine
cAMP
medicine
Animals
Humans
Testosterone
Receptor
Cells, Cultured
Bioassay
Dose-Response Relationship, Drug
Chemistry
urogenital system
Research
luteinizing hormone/choriogonadotropin receptor
Obstetrics and Gynecology
Leydig Cells
Luteinizing Hormone
Mice, Inbred C57BL
030104 developmental biology
Reproductive Medicine
Signal transduction
Gonadotropin
Luteinizing hormone
hormones, hormone substitutes, and hormone antagonists
Hormone
Developmental Biology
Signal Transduction
Subjects
Details
- ISSN :
- 14777827
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Reproductive biology and endocrinology : RBE
- Accession number :
- edsair.doi.dedup.....dd25dbff5485a92b5d834be4c151cc17