Estradiol induces vasoactive intestinal peptide and prolactin gene expression in the rat anterior pituitary independently of plasma prolactin levels.

It is well established that estrogens are potent stimulators of prolactin (PRL) secretion. It has also been demonstrated that estradiol (E2) can increase the expression and the anterior pituitary levels of the vasoactive intestinal peptide (VIP), a peptide which also acts as a potent PRL-releasing factor. It thus remained unknown whether the effects on pituitary VIP were due to E2 itself or to E2-induced hyperprolactinemia (HPRL). In order to test this hypothesis, various plasma PRL levels were induced in rats either with ectopic pituitary grafts, PRL secreting tumours or E2 implants, and VIP mRNA expression in the anterior pituitary was measured by in situ hybridization and Northern blot analyses. Whereas decreases in VIP mRNA can be observed in pituitaries of rats with pure HPRL, a 6-fold increase in VIP mRNA can be seen in E2-treated rats. E2 increased both 1.0 and 1.7 Kb VIP mRNA species. The presence of the graft in E2-treated rats significantly reduced the increase in VIPmRNA observed following E2. The direct stimulation by E2 of VIP mRNA expression was further demonstrated by the fact that statistical analysis of the data indicated that both E2 and graft were acting independently of each other, and that a new selective antiestrogen, RU 58668, almost totally blocked the effect of E2. Moreover, under similar experimental conditions, pituitary PRL mRNA levels were reduced in the graft group and a marked up-regulation was observed similarly in both E2 and in E2 rats bearing ectopic grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptor imaging of human diseases using radiolabeled peptides.

The peptide somatostatin and its analog octreotide play an important role in neoplasia where their actions have been shown to be mediated by specific somatostatin receptors located in the tumor tissue. The identification of a high density of SS receptors in vitro in different types of human tumors has provided completely new and attractive possibilities for their diagnostic localization in vivo. This can be achieved by intravenous injection of 123I-[Tyr3]-octreotide or 111In-DTPA-D-Phe1-octreotide in patients suspected of having SS receptor-positive tumors and by subsequent localization of the tumors with gamma camera scintigraphy techniques. Hot spots representing radioligand binding on SS receptor-positive tumors are visualized with this method. This new SS receptor imaging method may help the clinicians for the localization of the primary tumor and its metastases, for the staging of certain tumors, to predict a successful SS therapy, and as a prognostic or differential diagnostic marker. It may also be of use in non-tumoral pathologies, to localize selected inflammatory processes and to monitor anti-inflammatory therapy. Somatostatin receptor imaging represents the first example of the clinical use of a small peptide as an efficient in vivo diagnostic tool and may be considered as a paradigm for further research on the role and the potential diagnostic use of other peptide receptors in pathological states.

Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.

In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.