241. Relaxin and INSL3 receptors and their signaling in primary human myometrial cells
K. Heng A , R. Ivell A , P. Waagarachi B and R. Anand-Ivell AA School of Molecular and Biomedical Science and Research Centre for Reproductive, University of Adelaide, Adelaide, SA, Australia.
B Women’s and Children’s Hospital, Adelaide, SA, Australia.
Reproduction, Fertility and Development 20(9) 41-41 https://doi.org/10.1071/SRB08Abs241
Published: 28 August 2008
Abstract
In model species such as the pig or rat, the ovarian peptide hormone relaxin is able to induce uterine quiescence, suppressing natural or oxytocin-induced contractility via a cAMP-dependent mechanism. This is not observed in humans. The present study investigated the ability of relaxin to activate adenylate cyclase in primary human myometrial smooth muscle cells from non-pregnant tissue obtained at hysterectomy. We show that relaxin is indeed able to stimulate the generation of cAMP, and it does this in a manner which is dependent upon the mediation of a tyrosine phosphorylation activity as has been shown by us earlier in the endometrium and THP-1 cells, though likely not involving PI3-kinase. Furthermore, we identified transcripts for the relaxin receptor RXFP1 (formerly LGR7) as full-length variants, though a minor splice variant missing exon 2 was also present in low amounts. Interestingly human myometrial cells also express transcripts encoding the full-length receptor, RXFP2 (formerly LGR8), for the closely related peptide hormone, INSL3. This receptor can also respond to relaxin at high concentration. However, 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, therefore, the well known inability of relaxin to inhibit contractility in human myometrial cells appears to be due to uncoupling events downstream of cAMP generation.
Research supported by NH&MRC project grant 349502.
