Relaxin Regulation of Endometrial Structure and Function in the Rhesus Monkey

Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment o...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 13; pp. 4685 - 4689
Main Authors:	Goldsmith, Laura T., Weiss, Gerson, Palejwala, Smita, Plant, Tony M., Wojtczuk, Andrea, Lambert, W. Clark, Ammur, Nael, Heller, Debra, Skurnick, Joan H., Edwards, Dean, Cole, Donna M., Lieberman, Seymour
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 30-03-2004 National Acad Sciences
Subjects:	Anatomy & physiology Animals Biological Sciences Body Weight Connective tissues Endocrinology Endometrium Endometrium - anatomy & histology Endometrium - blood supply Endometrium - physiology Epithelial cells Estradiol - pharmacology Estrogen Receptor alpha Estrogen Receptor beta Estrogen receptors Female Hormones Humans Lymphocytes Macaca mulatta Mammals Monkeys & apes Neovascularization, Physiologic - drug effects Organ Size - drug effects Ovariectomy Pregnancy Primates Progesterone - pharmacology Progesterone receptors Proteins Receptors, Estrogen - antagonists & inhibitors Receptors, Estrogen - drug effects Receptors, Estrogen - physiology Relaxin - physiology Reproduction Uterus - anatomy & histology Uterus - drug effects
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Summary:	Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor α, but not β, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 To whom correspondence should be addressed. E-mail: goldsmit@umdnj.edu. Communicated by Seymour Lieberman, St. Luke's-Roosevelt Institute for Health Sciences, New York, NY, February 4, 2004 Abbreviations: TIMP, tissue inhibitor of metalloproteinase; MMP, matrix metalloproteinase; proMMP-1, procollagenase; proMMP-3, prostromelysin.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0400776101