Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Estrogen regulation of prodynorphin gene expression in the rat adenohypophysis: effect of the antiestrogen tamoxifen. 789 68

The effects in the brain of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have not yet been fully elucidated. Based upon the hypothesis that serotonin (5-HT)-steroid hormone interactions are important in mood regulation, we have compared six SERMs (tamoxifen, raloxifene, levormeloxifene, NNC 45-0781, NNC 45-0320, NNC 45-1506) with 17beta-estradiol (E(2)) in terms of their ability to regulate mRNA levels of estrogen receptor (ER)alpha, ER beta, 5-HT(1A) receptor, and 5-HT reuptake transporter (SERT) in the midbrain, amygdala, and hypothalamus of ovariectomized (OVX) rats. Female rats (n = 6/group, 8 groups total) were OVX and allowed to recover for 2 weeks. During the third post-OVX week, rats were injected subcutaneously with E(2) (0.1 mg/kg) or one of the SERMs (5 mg/kg) once per day for 7 days. Twenty-four hours after the last injection, tissue was collected for the determination of mRNA levels by ribonuclease protection assay (RPA). E(2) treatment significantly decreased mRNA levels for ER alpha, ER beta, and SERT in midbrain and ER alpha in hypothalamus. Tamoxifen increased ER beta mRNA levels in hypothalamus, while raloxifene increased ER beta mRNA levels in amygdala. NNC 45-0320 decreased ER alpha mRNA in hypothalamus and decreased ER beta mRNA in amygdala. These results suggest that while SERMs are not full estrogen receptor agonists in the brain, the agonist/antagonist profiles for individual SERMs may differ among brain areas. This raises the possibility of developing new SERMs for selective functions in specific brain areas.
 ...
PMID:Selective estrogen receptor modulator effects in the rat brain. 1181 32

The progesterone receptor (PR) has three isoforms, PR-A, PR-B, and PR-C, which have different physiological effects. PR-A may inhibit PR-B-mediated transcription. Parturition requires withdrawal of progesterone (P4). This could occur through decreased P4 concentrations and/or a change in PR isoforms to diminish the effect of P4. We measured mRNA for PR isoforms in rat uterine tissues through late gestation and investigated the effects of antagonists to estrogen (tamoxifen) and P4 (RU-486). Two specific probes were used for ribonuclease protection assays; one (PR-total) measured PR-A, PR-B, and PR-C, and the other recognized only PR-B. PR-total mRNA increased significantly through late gestation, whereas PR-B was unchanged. The ratio of PR-total to PR-B peaked on the day before parturition. Tamoxifen delayed parturition and inhibited the increase in PR-total without affecting PR-B mRNA. RU-486 caused early parturition associated with increased PR-total mRNA, with no change in PR-B. We conclude that there are significant changes in PR isoforms in late-gestation rat uterus. These changes may be regulated by estrogen and P4 and may influence the timing of parturition.
 ...
PMID:Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus. 1238 56