EXPRESSION OF PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) AND THE PTHPTHRP RECEPTOR IN THE RAT UTERUS DURING EARLY-PREGNANCY AND FOLLOWINGARTIFICIAL DECIDUOMA INDUCTION/

The interaction between parathyroid hormone-related protein (PTHrP) an d the parathyroid hormone (PTH)/PTHrP receptor is thought to play a ro le in the growth and differentiation of various tissues throughout fet al development in the rodent. The aim of the present study was to defi ne the patterns of expression of PTHrP and of the PTH/PTHrP receptor i n the rat uterus during the early stages of normal pregnancy, and foll owing artificial induction of a decidual reaction. Using hybridization histochemistry, we have shown that the receptor gene is switched on e arly in pregnancy (by 1.5 days post coitum) in the endometrial stromal cells that surround the lumen. These cells include the anti-mesometri al subepithelial stromal cells that are destined to become decidualize d. This pattern continues until 5.0 days post coitum, when PTHrP is sw itched on in antimesometrial luminal epithelial cells that line the im plantation chamber. Stromal cells underlying the implantation chamber then downregulate transcription of the receptor gene, and within 12 h differentiate into decidual cells. A similar pattern was seen in uteri in which a decidual reaction had been induced artificially. Therefore , it may be postulated that in early pregnancy the endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some time after receiving the signal, the endometrial stromal cells do wnregulate the receptor gene, and this appears to be a trigger for the terminal differentiation of the stromal cells into decidual cells. Th ese results suggest that PTHrP, acting through the PTH/PTHrP receptor, plays a role in the initiation of a decidual reaction during early pr egnancy by regulating the differentiation of endometrial stromal cells into decidual cells.