Ovine Placental Lactogen Specifically Binds to Endometrial Glands of the Ovine Uterus1

Abstract

A hormonal servomechanism has been proposed to regulate differentiation and function of the endometrial glandular epithelium (GE) in the ovine uterus during pregnancy. This mechanism involves sequential actions of estrogen, progesterone, ovine interferon tau (IFNtau), placental lactogen (oPL), and placental growth hormone (oGH). The biological actions of oPL in vitro are mediated by homodimerization of the prolactin receptor (oPRLR) and heterodimerization of the oPRLR and oGH receptor. The objectives of the study were to determine the effects of intrauterine oPL, oGH, and their combination on endometrial histoarchitecture and gene expression and to localize and characterize binding sites for oPL in the ovine uterus in vivo using an in situ ligand binding assay. Intrauterine infusion of oPL and/or oGH following IFNtau into ovariectomized ewes treated with progesterone daily differentially affected endometrial gland number and expression of uterine milk proteins and osteopontin. However, neither hormone affected PRLR, insulin-like growth factor (IGF)-I, or IGF-II mRNA levels in the endometrium. A chimeric protein of placental secretory alkaline phosphatase (SEAP) and oPL was used to identify and characterize binding sites for oPL in frozen sections of interplacentomal endometrium from pregnant ewes. Specific binding of SEAP-oPL was detected in the endometrial GE on Days 30, 60, 90, and 120 of pregnancy. In Day 90 endometrium, SEAP-oPL binding to the endometrial GE was displaced completely by oPL and prolactin (oPRL) but only partially by oGH. Binding experiments using the extracellular domain of the oPRLR also showed that iodinated oPL binding sites could be competed for by oPRL and oPL but not by oGH. Collectively, results indicate that oPL binds to receptors in the endometrial glands and that oPRL is more effective than oGH in competing for these binding sites. Thus, effects of oPL on the endometrial glands may be mediated by receptors for oPRL and oGH.

Bovine prolactin-related protein-I is anchored to the extracellular matrix through interactions with type IV collagen

“…A similar strategy was previously used to identify cellular targets for other PRL family ligands (Muller et al 1998, Lin & Linzer 1999, Wang et al 2000, Noel et al 2003.…”

Pregnancy recognition signals in mammals: the roles of interferons and estrogens

“…Studies on the role of IFNT in pregnancy identified a servomechanism for maintenance of pregnancy that requires reciprocal communication between the conceptus and endometrium during implantation and during synepitheliochorial placentation in ewes (Spencer et al, 1999Stewart et al, 2000Stewart et al, , 2001Noel et al, 2003). This concept derived from our studies to determine if the antiluteolytic effects of IFNT to extend lifespan of CL are reinforced by effects of placental lactogen (CSH1) and/or placental growth hormone (GH1) secreted from day 15 to term, and days 35 to 65 of pregnancy, respectively.…”

Advances in flow cytometry in basic and applied equine andrology

“…While some ruminants have a single placental lactogen, cattle have as many as 13 PRL-like genes (Ushizawa et al, 2007). Ovine placental lactogen (oPL) binds both to growth hormone (GH) and PRL receptors in the uterine glands thereby stimulating gland hyperplasia and secretion of histotrophe (Noel et al, 2003). There is sequential action on the glands of IFN-τ, oPL and ovine placental GH (Noel et al, 2003).…”

“…Ovine placental lactogen (oPL) binds both to growth hormone (GH) and PRL receptors in the uterine glands thereby stimulating gland hyperplasia and secretion of histotrophe (Noel et al, 2003). There is sequential action on the glands of IFN-τ, oPL and ovine placental GH (Noel et al, 2003). Placental lactogen may play a subsidiary role in corpus luteum maintenance (Buttle, 1978).…”