Maud Eriksson

Distribution and Coexistence of Corticotropin-Releasing Factor-, Neurotensin-, Enkephalin-, Cholecystokinin-, Galanin- and Vasoactive Intestinal Polypeptide/Peptide Histidine Isoleucine-Like Peptides in the Parvocellular Part of the Paraventricular Nucleus

The distribution of several peptides, corticotropin-releasing factor (CRF), neurotensin (NT), enkephalin (ENK), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), cholecystokinin (CCK), thyrotropin-releasing hormone (TRH) and galanin (GAL) was studied in detail with immunohistochemistry in the various subdivisions of the parvocellular part of the rat hypothalamic paraventricular nucleus (PVN). Using a double-staining method and elution-restaining technique, the coexistence of CRF- and NT-like immunoreactivities (LI) with other neuropeptides was analyzed. Our results indicate that coexistence of two or more peptides in the PVN is common, and revealed that about 30% of the CRF neurons contain NT-LI and about 20% ENK-LI, whereas other peptides only occur in small fractions of the CRF cells. Thus, it seems possible to define three major subpopulations of CRF neurons, one containing NT-LI, another one containing ENK-LI and a third one apparently lacking these peptides. Conversely, about 60% of both NT- and ENK-immunoreactive neurons lacked CRF-LI. A large proportion of the small population of VIP/PHI neurons contained NT-LI. TRH neurons represented a neuron population completely distinct from the CRF neurons. Also, it did not seem to contain any of the other peptides studied with the rare exception of ENK-LI. Neuropeptides present in the PVN and presumably in nerve fibers of the external layer of the median eminence may participate in the control of the anterior pituitary hormone secretion. Whereas the role of CRF and TRH is well established, the physiological role of the other peptides studied here is still unclear.

Evidence of a Peripheral and a Central Effect of Oxytocin on Pancreatic Hormone Release in Rats

The aim of the present study was to investigate how oxytocin given subcutaneously (SC) and intracerebroventricularly (ICV) influences the secretion of insulin, glucagon and glucose and to investigate whether the effect on these variables of suckling in lactating rats is mediated by oxytocinergic mechanisms. Male rats were given oxytocin in doses of 2 or 20 ng (SC) or 2 or 200 ng (ICV). Trunk blood was collected and hormone analysis performed by radioimmunoassay. Subcutaneous injections of oxytocin increased insulin, glucagon and glucose levels significantly. Two nanograms oxytocin given ICV had no effect on glucagon and glucose levels but caused a significant rise in insulin levels at this time point. This effect was abolished by atropine. The oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin administered ICV increased insulin levels itself and therefore the effect on oxytocin-induced insulin secretion was difficult to evaluate. Intracerebroventricular injections of 200 ng oxytocin caused a significant rise not only of insulin but also of glucagon and glucose levels. Since this dose of oxytocin also caused a substantial rise of circulating oxytocin levels, these effects on glucose and glucagon may have been exerted at a peripheral site. Suckling in lactating rats was followed by a significant increase of glucose and glucagon levels. These effects were completely abolished by pretreatment with an oxytocin antagonist. In conclusion, oxytocin seems to influence pancreatic hormone secretion by two different mechanisms. Elevated circulating levels of oxytocin-e.g. as seen in response to suckling in lactating rats-are accompanied by a rise of glucagon and glucose levels which is blocked by the oxytocin antagonist. In contrast, nanogram amounts of oxytocin administered ICV cause a rise of insulin levels. Since this effect was blocked by atropine, it is likely to involve activation of vagal cholinergic neurons, innervating pancreatic beta-cells.

Plasma levels of gastrin, somatostatin, and cholecystokinin immunoreactivity during pregnancy and lactation in dogs

Plasma levels of gastrinlike, somatostatinlike, and cholecystokininlike immunoreactivity were determined by radioimmunoassay in peripheral blood from 11 beagles during pregnancy and in response to suckling during lactation. Cholecystokinin was determined in pooled and in individual plasma samples after separation of cholecystokinin and gastrin by high-performance liquid chromatography. Gastrin and somatostatin levels were significantly increased during the 8-wk-long dog pregnancy; peak values were recorded in week 7 and week 4, respectively. The cholecystokinin level rose and peaked at week 3, and remained elevated. In response to suckling, maternal gastrin levels rose significantly when tested in week 1 and 3 of lactation. Somatostatin levels did not respond significantly to suckling, but basal levels were elevated in week 1 compared to week 3 of lactation. Cholecystokinin rose in response to suckling both in week 1 and 3 of lactation. We suggest that the increased levels of gastrointestinal hormones during pregnancy and lactation may serve to increase digestive and anabolic capacity.

Plasma levels of vasoactive intestinal polypeptide and oxytocin in response to suckling, electrical stimulation of the mammary nerve and oxytocin infusion in rats.

The aim of the present study was to measure plasma levels of vasoactive intestinal polypeptide (VIP) and oxytocin following suckling, electrical stimulation of the mammary nerve and oxytocin infusion in lactating rats. Trunk blood was collected by decapitation after 5 and 20 min of suckling in conscious lactating rats. Repeated blood samples were drawn from the carotid artery in anesthetized rats, in connection with suckling, oxytocin infusion (0.22 nmol/l/kg/h) and electrical stimulation of the mammary nerve (5 V, 5 Hz, 2 ms). VIP and oxytocin levels were measured by radioimmunoassay. In conscious rats, VIP levels rose significantly from 18 +/- 5 to 102 +/- 30 pM after 5 min of suckling and to 123 +/- 25 pM after 20 min of suckling when milk ejection occurred. Oxytocin levels rose significantly from 90 +/- 24 to 269 +/- 45 pM during milk ejection. Suckling, oxytocin infusion and mammary nerve stimulation in anesthetized rats raised VIP levels significantly from 13 +/- 2, 18 +/- 5 and 10 +/- 2 to 43 +/- 8, 45 +/- 16 and 53 +/- 22 pM, respectively, whereas oxytocin levels rose from 111 +/- 34 to 294 +/- 66 pM after 20 min of suckling and to a peak value of 500 +/- 70 pM after oxytocin infusion. This study shows that VIP is elevated in plasma in lactating rats when the pups are suckling. The results showing that VIP levels rise following mammary nerve stimulation and oxytocin infusions indicate that both neurogenic and hormonal mechanisms can contribute to the regulation of VIP levels in plasma.

Increased levels of vasoactive intestinal peptide (VIP) and oxytocin during suckling in lactating dogs

The aim of the present study was to investigate how suckling influences the plasma levels of oxytocin and vasoactive intestinal peptide in lactating dogs. Blood-samples were drawn from ten lactating beagles during suckling, in week one and week three of the five week long lactation period and the levels of vasoactive intestinal peptide and oxytocin were determined by radioimmunoassay. The immunoreactive levels of vasoactive intestinal peptide and oxytocin (below referred to VIP and oxytocin) increased rapidly in response to the suckling stimulus. The rise of both peptides was significant at both suckling experiments. The origin and role of suckling-released oxytocin is well established. The origin of and function of the VIP released in response to suckling remains unknown.