DNA synthesis by ovine mammary alveolar epithelial cells: effects of heparin, epidermal growth factor-related peptides and interaction with stage of pregnancy
| Autor: | Isabel A. Forsyth, C D Moorby, J A Taylor |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Mammary gland Cell Antineoplastic Agents Gestational Age Biology Amphiregulin Mammary Glands Animal Endocrinology Pregnancy Epidermal growth factor Microsomes Internal medicine medicine Animals Insulin Insulin-Like Growth Factor I Growth Substances Glycoproteins Hexadimethrine Bromide Analysis of Variance Sheep Dose-Response Relationship Drug Epidermal Growth Factor DNA synthesis Heparin Growth factor Drug Synergism Epithelial Cells DNA Transforming Growth Factor alpha medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Pregnancy Animal Female medicine.drug Transforming growth factor |
| Zdroj: | Journal of Endocrinology. 156:283-290 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe.0.1560283 |
| Popis: | Amphiregulin is a heparin-binding member of the epidermal growth factor (EGF) family, which we have recently shown to be expressed in sheep mammary gland. Uniquely among known EGF-like growth factors, its mitogenic activity is inhibited by soluble heparin, but heparin-like molecules on the cell surface and/or in extracellular matrix appear to be necessary for amphiregulin to exert its biological effect. In primary cultures of sheep mammary alveolar epithelial cells, heparin (1-20 mg/l) inhibited DNA synthesis in a dose-dependent manner. The extent of the inhibition was influenced by physiological state, being greater (P < 0.05) in mammary cell cultures derived from 5- to 10-week pregnant sheep (63.1 +/- 8.2%, mean +/- S.E.M., n = 8) than in cultures derived from sheep which were non-pregnant (35.8 +/- 8.3% inhibition, n = 6) or late, 20-week, pregnant (39.8 +/- 5.6%, n = 6). Both EGF and transforming growth factor-alpha (TGF-alpha) significantly (P < 0.001) increased DNA synthesis in the presence of heparin. The effect of TGF-alpha was dose-related, wholly reversing the inhibitory effect of heparin in cell cultures from non-pregnant and 20-week pregnant sheep. DNA synthesis was stimulated by amphiregulin and TGF-alpha increased the maximum response. The heparin antagonist, hexadimethrine, inhibited DNA synthesis, but, in the presence of amphiregulin, approximately equivalent concentrations of heparin overcame this inhibitory effect. In the presence of heparin, TGF-alpha showed synergistic interactions with insulin or IGF-I. The results indicate interactive effects of EGF and IGF growth factor families in sheep mammary growth. |
| Databáze: | OpenAIRE |
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