EFFECT OF ANTAGONISM OF THE PARATHYROID-HORMONE (PTH) PTH-RELATED PROTEIN-RECEPTOR ON DECIDUALIZATION IN RAT UTERUS/

Parathyroid hormone-related protein (PTHrP) was detected at 32.8+/-3.9 pmol l(-1) in uterine luminal fluid from immature rats treated with o estradiol. As mRNA encoding PTHrP has previously been localized to imp lantation sites in pregnant rats, the role of luminal PTHrP during pre gnancy was explored. Infusion of a parathyroid hormone (PTH)/PTHrP rec eptor antagonist, [Asn(10),Leu (11)]PTHrP(7-34) amide, into the uterin e lumen during pregnancy in rats resulted in excessive decidualization . This effect was also observed after intrauterine infusion of a monoc lonal antibody raised against PTHrP. The effect of infusion of PTH/PTH rP receptor antagonist was dependent upon successful implantation, was dose-dependent and confined to the treated hem. A decrease in the num ber of apoptotic decidual cells in antagonist-infused uterine hems com pared with vehicle or non-infused hems was detected immunohistochemica lly at day 13 of pregnancy, and this decrease is likely to contribute to the 'over-decidualization' observed. In pseudopregnant rats, infusi on of PTH/PTHrP receptor antagonist into the uterine lumen resulted in an increase in uterine wet weight of the infused hom compared with th e non-infused horn, indicating a direct effect on deciduoma formation. Thus, activation of the PTH/PTHrP receptor by locally produced PTHrP appears to be crucial for normal decidualization during pregnancy in r ats.