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Prodynorphin (Prodyn)-derived peptides are synthesized in a subset of gonadotrope cells and released concomitantly with LH and FSH, and their levels in the rat adenohypophysis are influenced by the gonadal steroid environment. In several hormonal systems, factors that affect peptide levels may modulate the transcription of messenger RNA (mRNA) encoding for the target gene. Therefore, the present study was designed to investigate the effects of gonadal ablation and estrogen replacement on changes in steady state levels of anterior pituitary Prodyn mRNA and on the transcription rate in the adult female rat. The antiestrogen tamoxifen was employed for further exploring the relationships between estrogens and dynorphin (dyn)-related peptides. Adopting a solution hybridization-ribonuclease protection assay, steady state levels of Prodyn mRNA doubled in 2-week ovariectomized (OVX) rats, in parallel with a 3-fold increase in immunoreactive dyn-A-(1-17)-like material (irdyn-A). Estradiol (E2) replacement through sc SILASTIC implants for 1, 3, 7, and 14 days, which produces serum E2 levels between 25-35 pg/ml, restored in a time-dependent manner mRNA and peptide concentrations to values in sham-OVX rats. A significant decrease was observed after 3 days, and after 7 days, the effect was maximal. Tamoxifen (250 micrograms/kg.day, sc) administered simultaneously antagonized the action of E2 on Prodyn gene expression. Tamoxifen administered without E2 for 7 or 14 days significantly raised anterior pituitary levels of Prodyn mRNA and ir-dyn-A. To establish whether E2 and tamoxifen exert their effects on adenohypophyseal Prodyn mRNA by influencing the transcriptional activity of this gene, an in vitro transcriptional elongation assay was performed on nuclei from the anterior pituitary. The transcriptional rate of the Prodyn gene was significantly increased in 2-week OVX rats. Prodyn mRNA synthesis was suppressed in OVX rats exposed to E2, an effect antagonized by tamoxifen administered concomitantly. The antiestrogen administered alone for 14 days further elevated the transcriptional rate of Prodyn mRNA induced by gonadal ablation. In conclusion, E2 down-regulated the synthesis of Prodyn-derived peptides in adenohypophyseal cells. The antiestrogen tamoxifen antagonized the effect of E2 and, when chronically administered to OVX rats, further elevated the postcastrational rise in Prodyn gene expression.

We evaluated plasma atrial natriuretic factor (ANF), beta-endorphin, met-enkephalin, dynorphin and noradrenaline levels in 20 healthy subjects and 20 acute congestive heart failure (CHF) patients. In all acute CHF patients plasma values of these hormones were higher than in healthy subjects. The hormonal pattern differed in patients with the more severe acute CHF (group 1) from patients with less severe acute CHF (group 2) (ANF 53.8 +/- 1.0 vs 34.6 +/- 1.5 pg.ml-1, noradrenaline 563.8 +/- 13.4 vs 202.4 +/- 10.6 pg.ml-1, met-enkephalin 41.0 +/- 3.2 vs 17.0 +/- 1.6 fmol.ml-1, dynorphin 46.8 +/- 3.7 vs 25.2 +/- 2.0 fmol.ml-1, P < 0.01; beta-endorphin 50.6 +/- 5.2 vs 41.8 +/- 4.1 fmol.ml-1,ns). Administration of an opioid antagonist (naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentration in healthy subjects. In group 1 naloxone administration significantly raised ANF (68.0 +/- 1.4 pg.ml-1), noradrenaline (776.6 +/- 18.7 pg.ml-1), blood pressure and heart rate, whereas in group 2 it significantly decreased ANF values (21.9 +/- 0.5 pg.ml-1) and did not modify the other parameters. Our findings suggest that the opioid system affects ANF release in acute CHF. In patients with severe CHF opioid peptides may attenuate ANF secretion reducing noradrenergic stimulation. On the other hand, when CHF is less severe and the sympathetic activity is moderate, opioid peptides may directly stimulate ANF secretion.

Plasma levels of beta-endorphin, met-enkephalin and dynorphin were assessed in acute myocardial infarction (AMI) patients, with and without pain (group I: no pain, N = 12; group II: severe pain, N = 16). Plasma opioid peptide concentration was measured on admission to hospital (between 1 and 3 h after the myocardial infarction onset), at 7, 12, 24 h and at 2, 3 and 4 days. A transient increase in plasma beta-endorphin levels was found in AMI patients with severe pain, the levels normalizing within 12-18 h when pain had ceased. No changes in beta-endorphin concentration were observed in AMI patients without pain. Compared with healthy subjects, low levels of met-enkephalin were found in both groups of AMI patients throughout the study. Low levels of dynorphin were observed in patients with no pain while in the other patients initial low levels of dynorphin normalized when pain ceased. Blood pressure, heart rate and central venous pressure values were normal and did not correlate with plasma opioid levels. The results suggest that endogenous opioids do not affect pain in the early phase of myocardial infarction. The rise in beta-endorphin concentration observed in patients with severe pain seems to be induced by pain stress.