Prolactin-Mediated Inhibition of 20α-Hydroxysteroid Dehydrogenase Gene Expression and the Tyrosine Kinase System

Autor: L. Zhong, T. G. Parmer, G. Gibori, M.C. Robertson
Rok vydání: 1997
Předmět:
Transcription
Genetic
endocrine system diseases
Placenta
Protein tyrosine phosphatase
Biochemistry
Receptor tyrosine kinase
Rats
Sprague-Dawley
Pregnancy
Cycloheximide
Enzyme Inhibitors
Tyrosine
Cells
Cultured
Labor
Obstetric
Janus kinase 2
biology
Protein-Tyrosine Kinases
STAT4 Transcription Factor
Genistein
DNA-Binding Proteins
medicine.anatomical_structure
Female
Corpus luteum
Tyrosine kinase
hormones
hormone substitutes
and hormone antagonists
endocrine system
medicine.medical_specialty
Biophysics
Gene Expression Regulation
Enzymologic
Corpus Luteum
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
RNA
Messenger
20-Hydroxysteroid Dehydrogenases
Molecular Biology
20-alpha-Hydroxysteroid Dehydrogenase
Granulosa Cells
Cell Biology
Janus Kinase 2
Isoflavones
FLT4
Molecular biology
Prolactin
Rats
Kinetics
Endocrinology
Trans-Activators
biology.protein
Zdroj: Biochemical and Biophysical Research Communications. 235:587-592
ISSN: 0006-291X
DOI: 10.1006/bbrc.1997.6833
Popis: The rat luteal 20alpha-hydroxysteroid dehydrogenase plays a key role at catabolizing progesterone and at decreasing the level of this steroid secreted by the ovaries. Throughout pregnancy and before parturition neither the mRNA nor the protein for this enzyme could be detected. In this investigation we set to examine whether PRL and PRL-like hormone from placental origin silence the expression of this gene and whether PRL action involves tyrosine kinase activity and/or de novo protein synthesis. The results revealed that PRL and PRL-like hormone from rat placental origin (rPL-1 and rPL-2), but not rat growth hormone, caused a rapid and profound inhibition of 20alpha-HSD mRNA expression in highly luteinized granulosa cells. Immunoprecipition and western blot analysis indicate that PRL-R associates with JAK2 and Stat5, and this association is increased within 30 seconds with PRL treatment. Although both JAK2 and Stat5 were phosphorylated on tyrosine upon PRL treatment, the PRL mediated inhibition of 20alpha-HSD was not reversed by either tyrosine kinase inhibitors, AG18 and genistein, but was largely reversed by the protein synthesis inhibitor cycloheximide. In summary, results of this investigation indicate that although PRL can activate the JAK2/Stat5 system in the corpus luteum, the down regulation of 20alpha-HSD mRNA by PRL does not appear to involve tyrosine kinase activity but depends on de novo synthesis of protein(s).
Databáze: OpenAIRE
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