Relaxin signalling in primary cultures of human myometrial cells.
In myometrium of pigs and rats, though not humans, relaxin appears to mediate an inhibition of spontaneous and oxytocin-induced contractility, presumably acting through a G-protein coupled receptor (RXFP1) to generate cAMP. In humans, circulating relaxin is highest in the first trimester, including the time of implantation, when transitory uterine quiescence could help a blastocyst to implant. We investigated whether relaxin can activate adenylate cyclase in primary human myometrial cells from non-pregnant tissue, and we show that relaxin is able to stimulate the generation of cAMP in a manner, which is dependent upon a tyrosine phosphorylation activity, as in the endometrium. We identified transcripts for the relaxin receptor RXFP1 as full-length variants, though a minor splice variant missing exon 2 was also present in low amounts. These cells also express transcripts encoding RXFP2, the receptor for the closely related hormone, INSL3. Although able to respond to relaxin at high concentrations, this receptor does not appear to function by contributing to the cAMP production in human myometrial cells, nor does INSL3 act as a functional agonist or antagonist of relaxin action. In conclusion, the inability of relaxin to inhibit contractility in human myometrial cells would appear to be due to events downstream of simple cAMP generation.
Heng
Kee
K
School of Molecular and Biomedical Science, University of Adelaide, Adelaide SA5005, Australia.
Ivell
Richard
R
Wagaarachchi
Prabhath
P
Anand-Ivell
Ravinder
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D012065:Relaxin / Q000494:pharmacology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C417543:RXFP1 protein, human; C472867:RXFP2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D005576:Colforsin; D012065:Relaxin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine