In vitro regulation of pituitary ACTH secretion in inflammatory disease susceptible Lewis (LEW/N) and inflammatory disease resistant Fischer (F344/N) rats.
Neuroendocrinology
; 56(4): 474-82, 1992 Oct.
Article
en En
| MEDLINE
| ID: mdl-1335552
We have previously shown that susceptibility to inflammatory disease in Lewis (LEW/N) rats is related to their limited hypothalamic-pituitary-adrenal (HPA) axis responses to a variety of inflammatory stimuli, while the relative resistance to inflammatory disease in Fischer (F344/N) rats is related to their potent HPA axis responses to these same stimuli. In vivo studies also showed that LEW/N pituitary ACTH responses to exogenous corticotropin-releasing hormone (CRH) were blunted compared to F344/N. To determine if there is a fundamental difference in pituitary corticotroph function between the two strains, independent of other factors influencing the HPA axis, we compared ACTH responses to a variety of stimuli in LEW/N and F344/N primary pituitary cell cultures. Here we show that in vitro basal ACTH secretion and peak ACTH response to CRH, forskolin and 8-bromo-cAMP are 50% lower in LEW/N than F344/N rats. However, these findings can be explained by other observations: diminished basal ACTH content, POMC mRNA, and a decreased number of corticotrophs, in pituitary cell cultures from LEW/N compared to F344/N rats. In addition, LEW/N corticotrophs were more sensitive to dexamethasone and to corticosterone suppression of CRH-stimulated ACTH secretion compared to F344/N. The data support the possibility of an HPA axis defect in LEW/N rats at the pituitary level which could be secondary to prolonged understimulation by hypothalamic CRH, or could also be partially related to enhanced glucocorticoid feedback inhibition.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hipófisis
/
8-Bromo Monofosfato de Adenosina Cíclica
/
Hormona Liberadora de Corticotropina
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Hormona Adrenocorticotrópica
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Glucocorticoides
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Neuroendocrinology
Año:
1992
Tipo del documento:
Article
Pais de publicación:
Suiza