Relaxin in paired samples of serum and milk from women after term and preterm delivery

While uterotrophic effects of relaxin are well documented, the mechanism through which relaxin promotes uterine growth is incompletely understood. Studies in rats suggest that relaxin-stimulated uterine edema depends on estrogen receptor (ER) activation. Here, neonatal pigs were used to investigate the interaction between relaxin and ER signaling pathways. Gilts were treated either at birth (postnatal day (PND) 0) (study 1) before the onset of endometrial ERa expression, or on PND 12 (study 2) after the onset of ERa expression. In study 1, gilts were treated with estradiol-17b or porcine relaxin for two days and uteri were collected on PND 2. In study 2, PND 12 gilts were treated with a single injection of the ER antagonist ICI 182,780 (ICI) or vehicle. Two hours later, gilts were given either estradiol-17b or porcine relaxin for two days. When administered for two days from birth (study 1), neither estradiol-17b nor relaxin affected uterine weight or protein content. However, uterine luminal epithelial height was greater in relaxin-than in vehicle-treated gilts. In contrast, in study 2, both estradiol and relaxin increased uterine weight, protein content and uterine luminal epithelial height on PND 14. These effects were inhibited by pre-treatment with ICI in both estradiol-and relaxin-treated gilts. The results indicate that uterotrophic effects of relaxin in the neonatal pig are related to age and to both the relative presence and state of activation of the ER system in developing uterine tissues between birth and PND 14.

Section: Discussionmentioning

confidence: 99%

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

“…Immunoreactive RLX was first identified in human colostrum within 3 days of parturition and in breast milk up to 6 weeks post partum (Eddie et al 1989). Since then, RLX has been detected in the colostrum/milk of several species (Goldsmith et al 1994) including the pig (Yan et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence for local RLX production in other tissues (Bryant-Greenwood et al 1980, Sakbun et al 1990. Evidence that RLX concentrations in milk are higher than in the maternal circulation (Sherwood et al 1981, Eddie et al 1989, Goldsmith et al 1994 suggests that RLX is either produced locally by the mammary gland or synthesized elsewhere and concentrated in milk.…”

Section: Introductionmentioning

confidence: 94%

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Characterization and biological activity of relaxin in porcine milk

Frankshun¹,

Ho²,

Reimer³

et al. 2011

A lactocrine mechanism for delivery of maternally derived relaxin (RLX) into the neonatal circulation as a consequence of nursing was proposed for the pig. Immunoreactive RLX was detected in colostrum and in the serum of newborn pigs only if they were allowed to nurse. Milk-borne RLX concentrations are highest during early lactation (9-19 ng/ml), declining to !2 ng/ml by postnatal day 14. Whether milk-borne RLX is bioactive is unknown. Evidence that RLX concentrations in milk are higher than in maternal circulation in several species suggests the mammary gland as a site of local RLX production. It is unknown whether the porcine mammary gland is a source of RLX. Therefore, objectives were to evaluate RLX bioactivity in porcine milk during the first 2 weeks of lactation, identify the form of RLX in porcine milk, and determine whether mammary tissue from early lactation is a source of milk-borne RLX. Milk RLX bioactivity was determined using an in vitro bioassay in which cAMP production by human embryonic kidney (HEK293T) cells transfected with the human RLX receptor (RXFP1) was measured. RLX bioactivity was highest at lactation day (LD) 0, decreasing to undetectable levels by LD 4. Immunoblot analysis of milk proteins revealed an 18 kDa band, indicating proRLX as the primary form of RLX in porcine milk. ProRLX protein and transcripts were detected in porcine mammary tissue on LD 0 and 7. Results support the lactocrine hypothesis by defining the nature and a potential source for bioactive proRLX in porcine colostrum/milk.

“…Relaxin, a milk-borne hormone, has been found in rodent, porcine, and human milk (Eddie et al 1989, Steinetz et al 1996, Yan et al 2006b). Bioactive relaxin is present in porcine milk (Frankshun et al 2009) and is detectable in the systemic circulation of newborn pigs only if they are allowed to nurse (Yan et al 2006b, Frankshun et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Chen¹,

Wiley²,

Ho³

et al. 2010

Disruption of estrogen-sensitive, estrogen receptor (ER)-dependent events during porcine uterine development between birth (postnatal dayZPND 0) and PND 14 affects patterns of uterine morphoregulatory gene expression in the neonate with lasting consequences for reproductive success. Uterine capacity for conceptus support is reduced in pregnant adult gilts exposed to estradiol valerate (EV) for 14 days from birth. Objectives here were to determine effects of EV exposure from birth through PND 13 on neonatal uterine and adult endometrial markers of growth, patterning, and remodeling. Targets included the relaxin receptor (RXFP1), estrogen receptor-a (ESR1) and vascular endothelial growth factor (VEGFA), morphoregulatory markers HOXA10 and WNT7A, and the matrix metalloproteinases (MMP)2 and MMP9. Gilts were treated daily with EV (50 mg/kg body weight per day, i.m.) or corn oil vehicle from birth through PND 13. Uteri were obtained from neonates on PND 14 and from adults on pregnancy day 12 (PxD 12). In neonates, EV exposure from birth increased uterine RXFP1 gene expression, and both ESR1 and VEGFA proteins. At PxD 12, endometrial RXFP1 mRNA remained elevated, while ESR1 protein was reduced. Early EV treatment decreased neonatal uterine WNT7A, but increased HOXA10 expression. WNT7A expression was reduced in EV-treated adults. Transient EV exposure increased MMP9 transcripts at PND 14, whereas both latent and active MMP9 activity was increased due to early EV treatment in adults on PxD 12. Results support the hypothesis that transient, estrogen-induced disruption of porcine uterine development from birth alters early programming events that lead to functional consequences in the adult.