Stanniocalcin (STC) in the Endometrial Glands of the Ovine Uterus: Regulation by Progesterone and Placental Hormones1

Abstract

Stanniocalcin (STC) is a hormone in fish that regulates calcium levels. Mammals have two orthologs of STC with roles in calcium and phosphate metabolism and perhaps cell differentiation. In the kidney and gut, STC regulates calcium and phosphate homeostasis. In the mouse uterus, Stc1 increases in the mesometrial decidua during implantation. These studies determined the effects of pregnancy and related hormones on STC expression in the ovine uterus. In Days 10-16 cyclic and pregnant ewes, STC1 mRNA was not detected in the uterus. Intriguingly, STC1 mRNA appeared on Day 18 of pregnancy, specifically in the endometrial glands, increased from Day 18 to Day 80, and remained abundant to Day 120 of gestation. STC1 mRNA was not detected in the placenta, whereas STC2 mRNA was detected at low abundance in conceptus trophectoderm and endometrial glands during later pregnancy. Immunoreactive STC1 protein was detected predominantly in the endometrial glands after Day 16 of pregnancy and in areolae that transport uterine gland secretions across the placenta. In ovariectomized ewes, long-term progesterone therapy induced STC1 mRNA. Although interferon tau had no effect on endometrial STC1, intrauterine infusions of ovine placental lactogen (PL) increased endometrial gland STC1 mRNA abundance in progestinized ewes. These studies demonstrate that STC1 is induced by progesterone and increased by a placental hormone (PL) in endometrial glands of the ovine uterus during conceptus (embryo/fetus and extraembryonic membranes) implantation and placentation. Western blot analyses revealed the presence of a 25-kDa STC1 protein in the endometrium, uterine luminal fluid, and allantoic fluid. The data suggest that STC1 secreted by the endometrial glands is transported into the fetal circulation and allantoic fluid, where it is hypothesized to regulate growth and differentiation of the fetus and placenta, by placental areolae.

Progesterone and interferon tau regulate leukemia inhibitory factor receptor and IL6ST in the ovine uterus during early pregnancy

“…The increase in endometrial LIFR expression by early treatment with P4 in study 2 also occurred coincident with early loss of PGR by endometrial LE/sGE (Satterfield et al 2006). Similarly, IL6ST is expressed predominantly in endometrial GE as is the case for secreted phosphoprotein 1 (commonly referred to as osteopontin), serpin peptidase inhibitor (also known as uterine milk protein or UTMP), stanniocalcin 1 (STC1), and GRP, which encode proteins secreted into the uterine lumen (Moffatt et al 1987, Ing & Roberts 1989, Johnson et al 1999b, Song et al 2006b, 2008b). All four of those genes are induced in endometrial GE by the long-term effects of continuous P4 that also requires loss of the PGR as a permissive event preceding IFNT effects to enhance gene expression (Spencer & Bazer 2002, Spencer et al 2004b.…”

Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

“…Sequential exposure of the pregnant ovine endometrium to progesterone, IFNT, and CSH1 appears to be required to activate and maintain endometrial remodeling, secretory function of GE, and perhaps uterine growth during gestation. Chronic treatment of ovariectomized ewes with progesterone induces SPP1, UTMP, and STC1 expression by GE (Moffatt et al 1987, Spencer et al 1999b, Johnson et al 2000b, Song et al 2006b). However, intrauterine infusions of CSH1 further increases endometrial SPP1, STC1, and UTMP gene expression, but only when ewes receive progesterone and intrauterine infusions of IFNT (Spencer et al 1999b, Noel et al 2003.…”

“…In pregnant ewes ( Fig. 1), loss of PGR in endometrial epithelia is associated with a reduction in anti-adhesive MUC1 (mucin glycoprotein 1) and onset LGALS15, CTSL, and CST3 expression in the LE (Gray et al 2004, Song et al 2005, 2006a, Satterfield et al 2006 and SPP1 (secreted phosphoprotein 1 or osteopontin), STC1 (stanniocalcin), and UTMP (uterine milk proteins or serpins) expression in the GE (Johnson et al Embryo-maternal communication 2000b, Stewart et al 2000, Song et al 2006b. One understudied area is what controls expression of the PGR and how PGR regulates transcription of target genes in a cell-specific manner within the uterus.…”

“…Placentae of many species, including rodents, humans, nonhuman primates, and ruminants, secrete hormones structurally related to pituitary prolactin (PRL) and growth hormone (GH) that are termed CSH1 (alias placental lactogen; Soares 2004). Ovine CSH1 is produced by trophoblast giant BNC from days 15 to 16 of pregnancy, which is coordinated with onset of expression of UTMP, SPP1, gastrin-releasing peptide (GRP), and STC1 (Ing et al 1989, Whitley et al 1998, Stewart et al 2000, Song et al 2006b), which are excellent markers for GE differentiation and secretory function during pregnancy in sheep (Fig. 1).…”

Placental Growth Hormone-Related Proteins and Prolactin-Related Proteins

“…oPL binds to endometrial PRLRs and increases the secretion of 'uterine milk' into the uterine lumen [52][53][54]. Stimulation of uterolactation does not require PL to enter maternal blood.…”