Prostaglandin F(2alpha) (PGF(2alpha)) and prolactin signaling: PGF(2alpha)-mediated inhibition of prolactin receptor expression in the Corpus luteum.
Endocrinology
; 144(8): 3301-5, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12865306
ABSTRACT
It is well established that prolactin (PRL) sustains, whereas prostaglandin F(2alpha) (PGF(2alpha)) curtails, progesterone production by the rodent corpus luteum (CL). We have previously shown that PGF(2alpha) inhibits the expression of several luteal genes stimulated by PRL, whereas it stimulates other genes inhibited by this hormone. We have also found that PGF(2alpha) stimulation of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), an enzyme that catabolizes progesterone, at the end of pregnancy is accompanied by a dramatic decrease in PRL receptor (PRL-R) expression. These findings, and the fact that the factors that inhibit PRL-R are not known, led us to examine in vivo whether the decline in PRL-R at the end of pregnancy is due to PGF(2alpha) and to also find out whether PGF(2alpha) opposes PRL action by inhibiting PRL-R expression. Using the PGF(2alpha) receptor (PGF(2alpha)-R) knockout, we examined whether the absence of the PGF(2alpha)-R prevents the decline in the expression of both the short and long forms of the PRL-R in the CL. We found that, in sharp contrast to the wild-type mice, in which both forms of the PRL-R decline to low levels between d 18-20 of pregnancy, expression of these receptors remained elevated in the PGF(2alpha)-R null mice. Furthermore, administration of PGF(2alpha) to pregnant rats inhibited PRL-R expression. Time-course analysis revealed that PGF(2alpha) treatment decreases both isoforms of PRL-R within 1 h of treatment in vivo, whereas its stimulatory effect on 20alphaHSD expression was further delayed. Similar results were obtained with luteinized granulosa cells in culture. To examine whether the decline in PRL-R is involved/necessary for PGF(2alpha) action, cells were transfected with a constitutively active PRL-R. The expression of this receptor did not prevent PGF(2alpha) effect on PRL-R or 20alphaHSD expression. Taken together, these results demonstrate that PGF(2alpha) inhibits the expression of the PRL-R and that the decline in both forms of the PRL-R that occurs at the end of pregnancy in the CL is due to PGF(2alpha). The results further suggest that PGF(2alpha)-mediated stimulation of 20alphaHSD is independent from PGF(2alpha) inhibition of PRL signaling in luteal cell.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prolactina
/
Receptores da Prolactina
/
Dinoprosta
/
Transdução de Sinais
/
Expressão Gênica
/
Corpo Lúteo
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Endocrinology
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA