Opposite effects of transforming growth factor alpha and epidermal growth factor on mouse placental lactogen I secretion.

Abstract

This study was undertaken to determine whether transforming growth factor a (TGF-a) regulates the production of mouse placental lactogen I (mPL-I) and mPL-II in a manner that is similar to that of epidermal growth factor (EGF), which was previously shown to stimulate mPL-I secretion and inhibit mPL-II secretion. In contrast to the activity of EGF, human (h) and rat (r) TGF-a (each at 100 ng/ml) inhibited secretion ofmPL-I by placental cells isolated from mice on day 7 of pregnancy. Maximum inhibition of mPL-I secretion occurred on the third day of a 5-day culture period and ranged between 37% and 56% in multiple trials. Incubation of cells with hTGF-a and EGF was not followed by a change in the mPL-I concentration of the medium, suggesting the peptides antagonized each other's effects. hTGF-a and rTGF-a inhibited secretion of mPL-II; maximum inhibition ranged between 62% and 84% in multiple trials. The lowest concentrations of hTGF-a that affected mPL-I and mPL-II secretion were 10 ng/ml and 1 ng/ml, respectively. EGF and hTGF-a bound to the same receptors on placental cells, as assessed by cross-linking, and both peptides stimulated receptor phosphorylation, as assessed by Western blot analysis.There are three types of mPL-containing cells in placental cultures: cells that contain only mPL-I, cells that contain only mPL-II, and cells that contain both mPLs. The percentage of each type of mPL-containing cell in the culture was determined by immunostaining. hTGF-ca affected the differentiation of the subpopulations of PL-containing cells in a manner that differed from that of EGF. The data suggest that TGF-a and EGF do not regulate the production of mPL-I and mPL-II in a similar manner.Transforming growth factor a (TGF-a) and epidermal growth factor (EGF) share 30-40% amino acid sequence homology and are believed to act by binding to a common receptor designated the EGF receptor (1, 2). As expected from their binding to a common receptor, effects of EGF and TGF-a have generally been similar, although qualitative and quantitative differences in the responses induced by the peptides have been observed (3-10). We recently examined effects of EGF on the secretion of mouse placental lactogen I (mPL-I) and mPL-II (11), which are prolactin-like hormones produced by trophoblast giant cells (12). mPL-I is present at high concentration in maternal blood on days 9 and 10 of pregnancy (13). mPL-II appears in maternal blood on day 9 of pregnancy and is present at relatively high concentration during the last week of pregnancy (term = 19 days) (14). EGF stimulated the secretion of mPL-I by mouse placental cells from days 7 and 9 of pregnancy and inhibited secretion of mPL-II by cells from days 7, 9, and 12. In addition, the sensitivity of mPL-II-producing cells to EGF declined between days 7 and 12 of pregnancy. These data suggested that EGF may play a role in the shift in placental PL production from mPL-I to mPL-II that occurs at midpregnancy. Effects of TGF-a in this system were not examined. Since TGF-a mRNA and/or...

Cited1 Is Required in Trophoblasts for Placental Development and for Embryo Growth and Survival

“…Some of these genes include those encoding TGF-␤1, TGF-␤3, activin A, inhibin, follistatin and nodal (dependent on Smad4), TGF-␣ (dependent on ER␣/␤), and adenosine deaminase and 3␤-hydroxysteroid dehydrogenase VI (dependent on TFAP2) (36,48,51,57). These factors have opposing effects on key processes during placental development: trophoblast proliferation and differentiation, and the promotion and inhibition of hormone and vasoactive factor secretion (76). We examined the expression of PLF and mPLII (which is potentially downstream of ER␣/␤), both of which are vasoactive factors, but could see no difference in the level of expression by RNA in situ hybridization.…”

Cytokines that Use gp130 as a Signal Transducer Stimulate Mouse Placental Lactogen-I (mPL-I) but Inhibit mPL-II Production in Vitro

“…Several factors regulate mPL-I and mPL-II secretion in vitro. Progesterone inhibits mPL-I secretion, whereas epidermal growth factor (EGF) and transforming growth factor a (TGFa) stimulate mPL-I secretion [1][2][3]. However, EGF, TGFa, interleukin-6 (IL-6), and tumor necrosis factor a (TNFa) all inhibit mPL-II secretion [2][3][4][5][6].…”

Development and function of trophoblast giant cells in the rodent placenta

“…In mice in which the pituitary gland is removed as the source of prolactin, secretion of both PL-I (Lopez et al, 1991) and PL-II (Kishi et al, 1988) is elevated and some milk production occurs indicating that the placental lactogens are partially sufficient to promote mammary development (Thordarson et al, 1989). PL-I and PL-II also have luteotrophic effects on the ovary and support progesterone production (Galosy and Talamantes, 1995;Thordarson et al, 1997). PL-I and PL-II can also increase insulin secretion (Brelje et al, 1993;Fleenor et al, 2000;Nielsen et al, 1999;Sorenson and Brelje, 1997) and stimulate an increase in the number of insulin producing β cells in pancreatic islets.…”

“…Several growth factors affect TGC differentiation and/or the expression of TGC-specific genes including Activin (Erlebacher et al, 2004), EGF (Yamaguchi et al, 1995), TGFβ (Erlebacher et al, 2004;Yamaguchi et al, 1995), IGF-I (Kanai-Azuma et al, 1993), IGF-II (Kanai-Azuma et al, 1993), and PTHrP (El-Hashash et al, 2005;El-Hashash and Kimber, 2006). Many of these factors exchange of nutrients and endocrine signals between mother and fetus.…”