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 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 alpha, but not beta, 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.
Goldsmith
Laura T
LT
Department of Obstetrics, Gynecology, and Women's Health, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. goldsmit@umdnj.edu
Weiss
Gerson
G
Palejwala
Smita
S
Plant
Tony M
TM
Wojtczuk
Andrea
A
Lambert
W Clark
WC
Ammur
Nael
N
Heller
Debra
D
Skurnick
Joan H
JH
Edwards
Dean
D
Cole
Donna M
DM
D000818:Animals; D001835:Body Weight; D004717:Endometrium / Q000033:anatomy & histology* / Q000098:blood supply / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D012065:Relaxin / Q000502:physiology*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol; D012065:Relaxin