Progesterone Maintenance of the Placental Progesterone Receptor and Placental Growth in Ovariectomized Rats1

Abstract

These studies examine the trophic effects of progesterone (P) on the progesterone receptor (Rp) and growth of the decidua basalis (DB) and junctional zone (JZ) in the rat placenta. Pregnant rats were ovariectomized (Ovx) in mid-pregnancy and received steroid replacement therapy consisting of implantation of P pellets (25 mg) and injections of estradiol (E), 2 micrograms s.c., daily. Placental protein synthesis, measured by 3H-leucine incorporation in vitro, decreased more than 99% within 24 h of Ovx. However, treatment with P immediately after castration maintained control levels of synthesis. Delay of P treatment for 4 h caused a 60% decline in protein production measured 20 h later (p less than 0.01). Intraperitoneal implantation of a 50-mg pellet of the antiprogestin, RU-38486, in intact pregnant rats decreased protein synthesis by 50% within 6 h and by more than 90% 12 h and 24 h post-implantation (p less than 0.01). Growth of DB and JZ in Ovx rats treated for 48 h with P and/or E was studied both histologically and by changes in protein and DNA content. Rp binding activity was also measured by exchange assay under equilibrium conditions. Only P was able to reverse the effects of Ovx on growth of the DB and JZ. P also maintained Rp levels in the DB above those observed in Ovx and Ovx + E-treated groups (p less than 0.01). The Rp may be a constitutive product in the JZ since binding activity was not altered by Ovx or by steroid treatments. This study shows that P is clearly a trophic hormone of the maternal and chorioallantoic placenta and is essential for placental growth, cellular differentiation, and histological integrity.

Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy

“…Alternatively, it is known that internucleosomal DNA fragmentation in the decidua basalis begins in mid-pregnancy (Ogle et al 1999). From day 14, the decidual tissue begins to regress to the end of pregnancy (Ogle et al 1990, Gu et al 1994. The controlled cell death of large numbers of decidual cells allows remodeling of the implantation chamber without disrupting the growth and development of the embryo or the integrity of the uterus (Welsh & Enders 1985).…”

Regulation of the Estrogen Receptor in the Decidua Basalis of the Pregnant Rat1

“…Estradiol was administered in 0.2 ml corn oil daily at one of three concentrations: 0.2, 0.75, or 2 ,pg, s.c. 4) OVX + vehicle: this group received only 0.2 ml corn oil, s.c. Serum was collected from each treatment group, and estradiol and progesterone were measured by RIA according to established procedures [24,28] to ascertain the level of circulating progesterone and estradiol produced by the hormonal regimens. The progesterone treatment regimen maintained a serum level consistent with pregnancy (114 ± 11 ng/ml) [24]. Injection of 0.2 plg estradiol resulted in a serum level of 0.11 0.04 ng/ml versus 0.08 + 0.07 ng/ml estradiol for intact pregnant animals on Days 10 and 14.…”

“…(Placentas from OVX and OVX + E treatment groups were severely degenerated, and separation of tissue types was problematic. Thus, our dissection procedures were considered to roughly divide the tissues into DB and JZ, with no LZ differentiated under these conditions [24]. Similarly, sufficient tissue could not be collected from OVX and OVX + E groups for ER determinations in studies using Day 8 pregnant rats because of extensive tissue necrosis.…”

“…Indeed, we have shown that a progesterone-dominated scheme of PR regulation occurs in the DB wherein progesterone but not estradiol maintains PR in ovariectomized (OVX) pregnant rats [24]. In fact, estrogendominated uterine stroma cells can be transformed to the progesterone-dominated scheme of PR regulation by chronic exposure to high levels of progesterone [25].…”

“…However, this system would be disastrously dysfunctional if it occurred in tissues responsible for maintenance of pregnancy (i.e., the decidua and chorioallantoic placenta). Chronic secretion of large amounts of progesterone is essential for the physiologic well-being of progestational tissues [20][21][22][23][24]. Thus, during pregnancy uterine tissues would become refractory to progesterone and rapidly regress if progesterone exerted an action similar to that described for the nonpregnant uterus.…”