CALBINDIN-D-9K GENE-EXPRESSION DURING THE PERINATAL-PERIOD IN THE RAT - CORRELATION TO ESTROGEN-RECEPTOR EXPRESSION IN UTERUS

Calbindin-D-9k (CaBP-9k) is a cytosolic calcium binding protein mainly expressed in duodenum. placenta and uterus. The gene encoding the rat CaBP-9k is subject to tissue specific induction by 1.25 dihydrosyvitamin D-3 (intestine) and estradiol (E(2)) (uterus). Control of placental expression remains unknown. The expression of CaBP-9k mRNA during the perinatal period was studied (pregnancy day 21 (P21)-lactation day 4 (L4). In uterus, maximal expression levels were found at P21 and maintained until L1. With the transition to L2 the CaBP-9k mRNA concentration dropped drastically below the detection limit as quantitated by Northern blot analysis. Measurements of E(2) and progesterone (P) levels showed a gradual decrease at late pregnancy (P21: birth). Post partum E(2) levels continued to decline and P concentrations increased slightly. Uterine estrogen receptor (ER) mRNA levels determined by cDNA/PCR analysis revealed close correlation between expression of ER and CaBP-9k mRNAs, ER mRNA levels were maximal at P22 and declined at parturition and with onset of lactation. At L2 and L3 ER mRNA levels were minimal and had decreased 5-fold compared to late pregnancy. CaBP-9k protein concentrations fluctuated only slightly dependent on the stage of the estrous cycle: estrus > proestrus > diestrus. During the perinatal period CaBP-9k concentration was overall lower than in non-pregnant uterus and revealed only a moderate increase at birth and decrease in early lactation. Similar to the uterine levels. placental CaBP-9k mRNA was highest at P21 and remained high until birth. Fetal duodenal CaBP-9k) rose sharply just prior to birth and plateaued in the early postpartal period. In maternal duodenum, no significant changes of CaBP-9k mRNA were found in the perinatal period. We conclude that CaBP-9k is tissue specifically regulated during the perinatal period and that in uterus, expression is dependent on a critical amount of ER and E(2).