S. Guller et al., DEVELOPMENTAL REGULATION OF GLUCOCORTICOID-MEDIATED EFFECTS ON EXTRACELLULAR-MATRIX PROTEIN EXPRESSION IN THE HUMAN PLACENTA, Endocrinology, 134(5), 1994, pp. 2064-2071
The extracellular matrix (ECM) protein fibronectin (FN) is a critical
regulator of uterine-placental adherence. In the present report we com
pared the effects of glucocorticoids on FN expression in cytotrophobla
st cultures isolated from human first trimester and term placentas to
elucidate potential steroid-dependent cellular mechanisms associated w
ith human parturition. Based on immunoassays, treatment of first trime
ster cytotrophoblasts with 10(-7) M dexamethasone (DEX) for 2 or 4 day
s reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an on
cofetal epitope) to approximately 80% of control levels. Conversely, t
reatment of cytotrophoblasts isolated from term placentas with DEX dra
matically reduced medium levels of onfFN to approximately 12% of contr
ol values. Treatment of both first trimester and term cells with 10(-6
) M progestin, mineralocorticoid, or estrogen had no significant effec
t on onfFN expression in either cell type. Glucocorticoids specificall
y down-regulated medium levels of onfFN in term cells, but not in firs
t trimester cells. In contrast, DEX treatment promoted an approximatel
y 3- to 7-fold increase in levels of hCG in both first trimester and t
erm cytotrophoblasts, suggesting that the effects of glucocorticoid on
FN and hCG expression are elicited through independent cell-signaling
pathways. In first trimester cells, DEX promoted a reduction in rates
of FN and laminin synthesis to 60-70% of control levels. In term cell
s, DEX treatment reduced levels of FN and laminin synthesis to approxi
mately 10% of control levels. Similarly, DEX treatment down-regulated
levels of FN mRNA to approximately 60% and 10% of control values in fi
rst trimester and term cells, respectively. The first trimester of hum
an pregnancy is associated with low levels of glucocorticoids and redu
ced glucocorticoid responsiveness. These conditions would favor high l
evels of placental ECM protein synthesis, thus stabilizing uterine-pla
cental adherence. Conversely, elevated levels of glucocorticoids near
parturition and increased glucocorticoid responsiveness would inhibit
placental ECM protein synthesis, reducing uterine-placental adherence
and promoting the separation of placenta from uterus.