Effect of estradiol on expression and activation of Akt protein in rat hypothalamus exposed to chronic [D-Met2, Pro5]-enkephalinamide treatment.
Adult ovariectomized rats were implanted with [D-Met2, Pro5]-enkephalinamide (ENK)-containing osmotic minipumps. Two hours prior to sacrifice, some animals were treated with estradiol-17beta (E2) at a dose 10 microg/100 g bodyweight (BW). Expression and activation of Akt proteins, nuclear [3H]estradiol binding, and the expression of estrogen receptor alpha (ERalpha) and beta (ERbeta) and of progesterone receptor (PR) were investigated. Estradiol increased the level of activated Akt protein (pAkt473) in the hypothalamus by 52 +/- 11% in comparison to the vehicle-treated controls. No such effect of E2 was observed 24 and 48 h after ENK implantation. This effect of ENK was abolished by concomitant treatment with naloxone. Time-dependent changes in nuclear [3H]estradiol binding and the expression of estrogen and progesterone receptors were also detected in the hypothalamus of ENK-implanted and E2-treated rats. At 24-48 h following ENK implantation, expression of ERalpha and high affinity [3H]estradiol binding decreased. At this time point, the PR level was also reduced, while the ERbeta level was augmented. In conclusion, these results suggest that the stimulatory effects of E2 on the expression and activation of Akt protein and the expression of ERalpha and PR are negatively regulated in rat hypothalamus exposed to chronic ENK treatment.
Vértes
Zsuzsanna
Z
Institute of Physiology, University Medical School of Pécs, 12 Szigeti Street, Pécs H-7643, Hungary. zsuzsanna.vertes@aok.pte.hu
Lengyel
Ferenc
F
Oszter
Angéla
A
Környei
József L
JL
Sumegi
Balázs
B
Vértes
Marietta
M
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D004343:Drug Implants; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D007700:Kinetics; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010052:Ovariectomy; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000378:metabolism; D013997:Time Factors
D004343:Drug Implants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009292:Narcotic Antagonists; D009294:Narcotics; D011518:Proto-Oncogene Proteins; D011980:Receptors, Progesterone; D009270:Naloxone; D004958:Estradiol; D004744:Enkephalin, Methionine; C021717:enkephalin, Met(2)-ProNH2(5)-; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt