Effects of Relaxin on Neonatal Porcine Uterine Growth and Development

Abstract

Relaxin (RLX), a key reproductive hormone in pigs, stimulates uterine growth in pregnant and prepubertal gilts and in neonates 2 weeks after birth. The neonatal uterotrophic response to RLX is developmentally regulated and estrogen receptor dependent because RLX fails to increase uterine weight in the absence of estrogen receptor (ER)-alpha or when the ER is chemically inactivated. However, the role of RLX and insulin-like peptide-3 receptors, LGR7 and LGR8, respectively, in the neonatal uterotrophic response is unknown. Current studies focus on direct (LGR7/8-mediated) and indirect (ER-mediated) effects of RLX in the neonatal porcine uterus. Porcine LGR7 and LGR8 cDNAs were cloned and used as probes to identify uterine transcripts for LGR7 and LGR8, which increased from birth (postnatal day [PND] 0) to PND 14, a critical period for porcine uterine development. In situ hybridization showed that endometrial signals for both LGR7 and LGR8 are predominantly stromal during this period. Administration of RLX on PND 0, before onset of uterine ER expression, increased uterine luminal epithelial height (P < .05) but not uterine weight in the LGR7/8-positive uterus on PND 2. However, RLX increased both uterine weight and luminal epithelial height by PND 14 (P < .05), after overt endometrial ER expression. Aberrant ER activation between PND 0 and 14 alters the uterine organizational program and affects the function of adult porcine uterine tissues. Present data suggest that crosstalk between LGR7/8 and ER may be involved in estrogen-sensitive morphoregulatory events that are central to the development of an optimally functional adult uterus in the pig.