Inhibition of growth in vitro by glucocorticoids in mouse embryonic facial mesenchyme cells

Salomon, David; Pratt, Robert M.

doi:10.1002/jcp.1040970306

Cited by 61 publications

(16 citation statements)

References 42 publications

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“…6-AN is a niacin antimetabolite teratogen that compromises NADPH supply by inhibition of the pentose pathway with downstream effects on potassium channels (Gupte et al, 2002) and redox pathways (Gupte et al, 2003). It is possible that cell death connects the two, since HC caused decreased cell number and thymidine incorporation in cultured A/J mesenchymal cells (compared to such cells from C57BL/6J; Salomon and Pratt, 1978), although Shimizu et al (2001) suggested an inhibition of apoptosis at the palatal shelf edge. We observed a very high correlation in susceptibility to these two teratogens among RI lines.…”

Section: Introductionmentioning

confidence: 93%

Correlation of susceptibility to 6-aminonicotinamide and hydrocortisone-induced cleft palate

Erickson¹,

Károlyi²,

Diehl³

2005

Life Sciences

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Section: Introductionmentioning

confidence: 93%

Correlation of susceptibility to 6-aminonicotinamide and hydrocortisone-induced cleft palate

Erickson¹,

Károlyi²,

Diehl³

2005

Life Sciences

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“…The total binding of labeled glucocorticoid to palatal and other embryonic tissue proteins varied in different strains of mice and correlated with the teratologic responsiveness of the strains to glucocorticoids. Salomon and Pratt (5,(28)(29)(30) demonstrated that mouse embryonic palatal mesenchyme cells possess high affinity, specific receptor proteins for glucocorticoid. The synthetic glucocorticoids dexamethasone and triamcinolone acetonide (TA) have a higher affinity for these receptors than the natural glucocorticoid hydrocortisone (HC), and a structure-activity study has shown that their affinity correlated well with their teratogenicity (31); TA was found to be 40 times as potent as HC and twice as potent as DEX (32).…”

Section: Glucocorticoid-induced Cleft Palatementioning

confidence: 99%

Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate.

Pratt¹

1985

Environ Health Perspect

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Glucocorticoids (triamcinolone) and dioxins (TCDD) are highly specific teratogens in the mouse, in that cleft palate is the major malformation observed. Glucocorticoids and TCDD both readily cross the yolk sac and placenta and appear in the developing secondary palate. Structure-activity relationships for glucocorticoid-and TCDD-induced cleft palate suggest a receptor involvement. Receptors for glucocorticoids and TCDD are present in the palate and their levels in various mouse strains are highly correlated with their sensitivity to cleft palate induction. Receptors for glucocorticoids appear to be more prevalent in the palatal mesenchymal cells whereas those for TCDD are probably located in the palatal epithelial cells. Glucocorticoids exert their teratogenic effect on the palate by inhibiting the growth of the palatal mesenchymal cells whereas TCDD alters the terminal cell differentiation of the medial palatal epithelial cells. Glucocorticoid-Induced Cleft PalateGlucocorticoids administered to several species of experimental animals at midgestation inhibit complete formation of the secondary palate (1-4). Development of the mammalian secondary palate is a complex process that depends upon the presence of various hormones and growth factors (5). The palatal shelves first appear as outgrowths from the maxillary process and subsequently grow in a vertical position alongside the tongue. The shelves undergo a rapid reorientation to the horizontal position above the tongue which brings the apposing epithelia into contact at the midline. The medial epithelial cells then undergo a programmed cell death with resorption ofthe basement membrane and cell remnants, and the two shelves fuse into a single tissue, the secondary palate, which separates the oral and nasal cavities (6,7).Different strains of inbred mice exhibit different degrees of susceptibility to glucocorticoid-induced cleft palate (1,8 (5,11,12). Walker and Fraser (6) showed that during normal development, the palatal shelves became horizontal later in the A/J than the C57BL/6J strain and suggested that this difference makes A/J mice more susceptible to cortisone than C57BL/6J mice (13). A recent study utilizing frozen sections (14) showed that, in addition to delaying palatal shelf elevation, cortisone treatment severely reduced the extent of contact between the palatal shelves in A/J mice. Although contact was present in 20% of the cortisone-treated fetuses, the mean area of the shelf contact was only 20% of that in control palates. Therefore, the net shelf contact in cortisone-treated litters was only 4% of the potential contact in control litters. Other studies in which shelf contact was assessed in glucocorticoid-treated fetuses reported contact in 27-30% of the fetuses. However, this limited contact, observed between the shelves in the midpalate region, was considered adequate for complete palatal fusion, and a failure in the fusion mechanism was proposed as an alternative (4,15). Diewert and Pratt (14) also observed shelf contact in the midpalate re...

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“…Studies of mechanisms of teratogen action have noted that several agents capable of producing palatal clefts in animals are also capable of inhibiting cell proliferation in the palate (e.g., retinoids, glucocorticoids, phenytoin; refs. 18,32,33). Treatment of pregnant animals with such agents at critical times during palatogenesis leads to the formation of small palatal shelves that fail to make contact and fuse.…”

Section: Introductionmentioning

confidence: 97%

Cross-talk between signaling pathways in murine embryonic palate cells: Effect of TGFβ and cAMP on EGF-induced DNA synthesis

Weston

Potchinsky

Lafferty

et al. 1998

In Vitro Cell.Dev.Biol.-Animal

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Signaling pathways utilized by EGF, cAMP, and TGF beta have been demonstrated to play critical roles in normal palate development. Stimulation of these pathways has been shown in palate cells and numerous other systems to affect cell growth. Because proper regulation of cell growth is critical to palate development, we speculate that fine regulation of palatal cell growth may be accomplished through crosstalk between these signaling pathways. We therefore set out to determine the effects of cAMP and TGF beta on EGF-induced cell proliferation in murine embryonic palate cells. We found that both TGF beta and cAMP inhibited the proliferative response of cells to treatment with EGF, whereas H89, a serine/ threonine protein kinase inhibitor with selectivity towards cAMP-dependent protein kinase, increased the cells' proliferative response to EGF. Genestein, a selective inhibitor of tyrosine kinases, at high doses abrogated the cells' proliferative response to EGF, confirming that EGF's ability to induce cell proliferation is critically dependent upon tyrosine kinase activity. Lower doses of genestein, however, actually enhanced cellular response to EGF. The data suggest that both the TGF beta- and cAMP-mediated signaling pathways may be involved in modulation of the effects of EGF on palate cell growth in vivo.

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Inhibition of growth in vitro by glucocorticoids in mouse embryonic facial mesenchyme cells

Cited by 61 publications

References 42 publications

Correlation of susceptibility to 6-aminonicotinamide and hydrocortisone-induced cleft palate

Correlation of susceptibility to 6-aminonicotinamide and hydrocortisone-induced cleft palate

Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate.

Cross-talk between signaling pathways in murine embryonic palate cells: Effect of TGFβ and cAMP on EGF-induced DNA synthesis

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