Endocrine effects of relaxin overexpression in mice

Shu Feng, Natalia V. Bogatcheva, Aparna A. Kamat, Anne Truong, Alexander I. Agoulnik

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-414
Number of pages8
JournalEndocrinology
Volume147
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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    Feng, S., Bogatcheva, N. V., Kamat, A. A., Truong, A., & Agoulnik, A. I. (2006). Endocrine effects of relaxin overexpression in mice. Endocrinology, 147(1), 407-414. https://doi.org/10.1210/en.2005-0626