Transmission of Relaxin from Lactating Bitches to their Offspring Via Suckling1

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

“…Relaxin (RLX), a prototypical milk-borne peptide hormone , is found in the colostrum of several species including humans (Eddie et al 1989), dogs (Goldsmith et al 1994), rats ), and pigs (Yan et al 2006). Immunoreactive RLX is detectable in the systemic circulation of newborn pigs only if they are allowed to nurse (Yan et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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.

“…our model it would be unaffected unless the pups take up RLFi during suckling. It has been shown in beagles that the hormone relaxin reaches the pups through the milk (Goldsmith et al 1994). Although RLFi effectively inhibits intra-abdominal migration of the testis in a dose-dependent manner, complete inhibition as described for the RLF (Insl3; Nef & Parada 1999, Zimmermann et al 1999 or GREAT (Lgr8; Overbeek et al 2001) knockout mouse has not been observed.…”

Section: Discussionmentioning

confidence: 98%

Cryptorchidism induced in normal rats by the relaxin-like factor inhibitor

Büllesbach¹,

Boockfor²,

Fullbright³

et al. 2008

Cryptorchidism is a serious problem, which affects 2-5% of the male population. Failure of the testes to descend into the scrotal region impairs germ cell development and is associated with a greater incidence of testicular cancer. The relaxin-like factor (RLF or insulin-like-3) has been shown to be critically important for the timely descent of the testicles in mice. We have discovered that the signal initiation site of the RLF can be eliminated without measurable effects on hormone binding to its receptor and that the resulting RLF derivative is a competitive inhibitor of RLF called RLFi. RLFi administered to pregnant rats causes dose-dependent gonadal retention in the offspring. The ability to control the severity of the syndrome by altering the concentration of RLFi and the timing of administration enables us to study in detail the structural changes that are associated with the action of RLF during critical stages of development. Targeted inhibition of the physiological migration pattern of testicles by RLFi lets one dissect the physiological process such as to find a window for clinical application of RLF and to search for ancillary factors that might play a role during normal development.