Trichostatin A specifically stimulates gonadotropin FSHß gene expression in gonadotroph LßT2 cells.
Endocr J
; 61(4): 335-42, 2014.
Article
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| MEDLINE
| ID: mdl-24430728
ABSTRACT
Trichostatin A (TSA) is a selective inhibitor of mammalian histone deacetylase. In the present study, TSA was found to selectively increase gene expression of the pituitary gonadotropin ß-subunit of follicle-stimulating hormone (FSH). Stimulation of mouse pituitary gonadotroph cell lines, LßT2, with TSA for 24 h resulted in no change in mRNA expression of the α- and LHß-subunit. On the other hand, FSHß-subunit mRNA expression was significantly increased in a dose-dependent fashion. Similarly, specific induction of the FSHß-subunit gene with TSA stimulation was observed in primary cultures of rat pituitary cells. Histone acetylation in whole cell lysates of LßT2 cells was significantly increased after TSA treatment, but not gonadotropin-releasing hormone (GnRH) treatment. The effect of TSA on FSHß mRNA expression was prominent compared to that of GnRH; however, TSA-stimulated FSHß mRNA expression was significantly reduced with combined TSA and GnRH treatment. TSA caused a slight increase in extracellular signal-regulated kinase (ERK) phosphorylation, while GnRH-increased ERK phosphorylation was potentiated in the presence of TSA. In addition, TSA, but not GnRH, significantly stimulated gene expression of retinaldehyde dehydrogenase 1 (RALDH1), a retinoic acid (RA) synthesizing enzyme involved in cell differentiation. These findings demonstrate that TSA specifically increases FSHß subunit gene expression with a concomitant increase in whole cell histone acetylation. Moreover, although GnRH is a stimulator of FSHß gene expression, it interfered with the stimulatory effect of TSA on FSHß mRNA expression, without modification of TSA-increased whole cell histone acetylation. This suggests that the mechanisms of TSA and GnRH-induced gonadotropin subunit gene expression are entirely distinct.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Hormona Folículo Estimulante de Subunidad beta
/
Gonadotrofos
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Inhibidores de Histona Desacetilasas
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Ácidos Hidroxámicos
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Endocr J
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón