Endocrine effects of relaxin overexpression in mice.
Relaxin is a small peptide hormone with a variety of biological functions. To investigate the systemic endocrine effects of relaxin, we produced mice with transgenic overexpression of the Rln1 gene, Tg(Rln1), driven by rat insulin 2 promoter. The expression of relaxin was detected in the pancreas of the transgenic animals. An analysis of the sera from the transgenic animals revealed at least 20-fold elevation of the level of bioactive relaxin. Transgenic animals had normal viability and fertility in both sexes. Transgenic overexpression of Rln1 did not rescue the undescended testis phenotype in Insl3-deficient males, suggesting that in vivo relaxin does not interact with the insulin-like 3 factor receptor, leucine-rich repeats-containing G protein-coupled receptor 8, Lgr8. Phenotypically, the excess of relaxin resulted in hypertrophic nipple development in virgin female mice. Deletion of the relaxin receptor, leucine-rich repeats-containing G protein-coupled receptor 7, Lgr7, in Tg(Rln1) animals abrogated the development of enlarged nipples in females, indicating that relaxin exerts its effect through Lgr7 alone. The levels of previously defined targets of relaxin signaling, such as matrix metalloproteinases 2 and 9, vascular endothelial growth factor, or nitric oxide, were similar in the sera of the transgenic and wild-type mice. However, the total plasma protein concentration in male Tg(Rln1) mice was lower than that in control animals. The livers of male Tg(Rln1) mice exhibited significantly higher hydroxyproline content, indicative of increased collagen deposition. Our results indicate that relaxin overexpression causes gender-specific changes in liver collagen metabolism.
Feng
Shu
S
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Bogatcheva
Natalia V
NV
Kamat
Aparna A
AA
Truong
Anne
A
Agoulnik
Alexander I
AI
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007328:Insulin / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D012065:Relaxin / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007328:Insulin; D012065:Relaxin; D003094:Collagen; D006909:Hydroxyproline