Posterior Pituitary Peptide Research Articles

Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management.

Diabetes insipidus (DI) is an endocrine condition involving the posterior pituitary peptide hormone, antidiuretic hormone (ADH). ADH exerts its effects on the distal convoluted tubule and collecting duct of the nephron by upregulating aquaporin-2 channels (AQP2) on the cellular apical membrane surface. DI is marked by expelling excessive quantities of highly dilute urine, extreme thirst, and craving for cold water. The two main classifications of DI are central diabetes insipidus (CDI), characterized by a deficiency of the posterior pituitary gland to release ADH, and nephrogenic diabetes insipidus (NDI), characterized by the terminal distal convoluted tubule and collecting duct resistance to ADH. The two less common classifications include dipsogenic DI, characterized by excessive thirst due to a low osmotic threshold, and gestational DI, characterized by increased concentration of placental vasopressinase during pregnancy. Treatment of DI is dependent on the disease classification, but severe complications may arise if not tended to appropriately. The most important step in symptom management is maintaining fluid intake ahead of fluid loss with emphasis placed on preserving the quality of life. The most common treatment of CDI and gestational DI is the administration of synthetic ADH, desmopressin (DDAVP). Nephrogenic treatment, although more challenging, requires discontinuation of medications as well as maintaining a renal-friendly diet to prevent hypernatremia. Treatment of dipsogenic DI is mainly focused on behavioral therapy aimed at regulating water intake and/or administration of antipsychotic pharmaceutical therapy. Central and nephrogenic subtypes of DI share a paradoxical treatment in thiazide diuretics.

Effect of Peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the Morphology of the Thymus in Hypophysectomized Young and Old Birds

Investigations were carried out on chicks of different age. It was found that the most pronounced changes in the morphology of the thymus occurred after neonatal hypophysectomy. These changes are least pronounced in old chicks. Peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis of amino acid composition of peptide complexes of the anterior and posterior pituitary lobes administered to hypophysectomized birds regardless of age promoted recovery of the morphological structures of the thymus. The anterior pituitary peptide (Lys-Glu-Asp-Gly) had more pronounced effect on the recovery of thymic structure than posterior pituitary peptide (Ala-Glu-Asp-Gly).

Reduction and S-nitrosation of the neuropeptide oxytocin: Implications for its biological function

Oxytocin (OT; Cys-Tyr-Ile-Gln-Asn-Cys-Pro-leu-Gly), a posterior pituitary peptide hormone, is characterized by a Cys1−Cys6 disulfide bond in its stable, isolated state. This paper describes a simple, one-step method for the production of OT in its reduced, dithiol form (OT dithiol), free of reducing agent. The effects of temperature, pH, and metal–ion chelators on the autoxidation of OT dithiol were examined to establish if this form is likely to persist under biological conditions. It was found that OT dithiol has a half-life of 1.8 h with respect to reformation of OT disulfide at 37 °C and pH 6.9 in the presence of the copper chelators, DTPA and neocuproine. S-Nitrosation of OT dithiol by acidified nitrite at pH 3.0 was examined by absorption spectroscopy and HPLC-UV-MS, which revealed that both singly and doubly S-nitrosated OT are formed. These results suggest novel chemical aspects to OT signaling, the biological implications of which are discussed here.

Effects of oxytocin, arginine-vasopressin and lysine-vasopressin on insulin and glucagon secretion in sheep

The effects of the posterior-pituitary peptides oxytocin ( ot), arginine-vasopressin ( avp) and lysine-vasopressin ( lvp) on insulin and glucagon secretion were examined in adult sheep. Each peptide was injected intravenously at doses from 1 to 3000 pmol kg −1. All three peptides increased plasma insulin and glucagon concentrations, but their dose-response relationships revealed differences between them. The maximal insulin responses induced by OT and AVP were very similar, but the threshold and maximal doses of avp for increasing plasma insulin were higher than those of OT. OT and AVP had the same activity for stimulating glucagon secretion in respect of the threshold and maximal doses and the maximal hormone response. lvp also increased plasma insulin and glucagon concentrations, but it had the weakest activity for stimulating both hormones. These results suggest that in sheep posterior-pituitary peptide may play a role in regulating nutrient metabolism by influencing pancreatic hormone secretion.

The duration of estradiol and progesterone exposure prior to progesterone withdrawal regulates oxytocin mrna levels in the paraventricular nucleus of the rat

The nonapeptide oxytocin (OT) is important for milk ejection during lactation, uterine contractility at parturition, and the onset of maternal behavior. Sequential exposure to estradiol (E2) and progesterone (P) followed by P withdrawal increases OT mRNA in the paraventricular nucleus (PVN), and to a lesser degree the supraoptic nucleus (SON), of the rat 48 hours after the P is removed. Although increases in PVN OT mRNA are not accompanied by changes in posterior pituitary OT peptide content, the PVN contains OT neurons that project to both the posterior pituitary (magnocellular group) and extra pituitary sites (parvocellular groups). Steroid-induced increases in OT mRNA occur in both the magnocellular and the parvocellular regions of the PVN. The latter are believed to contribute to CNS release of OT which may be important for certain behaviors including the onset of maternal behavior. The same steroid sequence that increases PVN OT mRNA also induces maternal behavior in virgin ovariectomized rats. Exposure of animals to E2 and P for 2 weeks resulted in the shortest latency to the onset of maternal behavior in ovariectomized rats, whereas exposure for 6 days was associated with a longer latency. In this study we questioned if the duration of E2 and P exposure prior to P withdrawal is an important regulator of PVN OT mRNA levels. We compared OT mRNA levels in the PVN of virgin ovariectomized rats administered no steroid or sequential E2 and P for 2 weeks versus 6 days. On day 1 animals received steroid-filled or empty capsules followed by P-filled or empty capsules on day 3. In one steroid-treated group, E2 and P were continued for 6 days and in the other group for 14 days prior to P removal. Animals were sacrificed 48 hours after P removal. Levels of OT mRNA were compared among 6 day and 2 week steroid-treated animals and sham-treated animals. The relative abundance of OT mRNA was significantly increased, P < 0.05, in animals receiving the 2-week, but not the 6-day, steroid treatment compared to sham-treated animals. Pituitary OT peptide content was not significantly different among the three groups. We conclude that the duration of steroid exposure may be an important regulator of the level of OT mRNA in the PVN of the rat.

Dissociation between vasopressin and oxytocin mRNA and peptide secretion after AV3V lesions

The effect of hypertonic NaCl consumption on vasopressin (VP) and oxytocin (OT) mRNA levels and plasma and pituitary peptides was evaluated in rats with sham or anterior ventral third ventricular (AV3V) lesions. Rats were given tap water or 2% NaCl for 4 days. Because the rats with lesions drank significantly less salt solution than the controls (78.8 +/- 17.4 vs. 205.5 +/- 37.8 ml/4 days), a second control group was included in which saline intake was matched to the lesioned group. AV3V rats showed a deficit in the peptide response to the osmotic stimulus. There was no increase in plasma VP or OT or decrease in posterior pituitary peptide content in the face of an extreme hypernatremia: plasma sodium of 180.1 +/- 4.2 meq/l. Evaluation of mRNA changes by means of in situ hybridization showed that animals with lesions responded to the salt challenge with increases in hypothalamic VP and OT mRNA levels. There were significant increases in paraventricular and supraoptic OT mRNA and paraventricular VP mRNA in the lesioned group. The salt-matched control group showed no changes in peptide mRNA levels. These results demonstrate that AV3V lesions produce an impairment of the salt-neuroendocrine reflex but a persistence of the peptide mRNA response. Differences in control mechanisms must account for this dissociation between peptide mRNA expression and peptide secretion.

Sinoaortic denervation alters the molecular and endocrine responses to salt loading.

Neuroanatomical and physiological evidence indicates that baroreceptors influence hypothalamic vasopressin (VP) and oxytocin (OT) neurons. We evaluated the effects of sinoaortic denervation (SAD) on the molecular and endocrine response to salt loading. Sham-operated or SAD rats were given a 2% NaCl solution to drink for 72 h. A group with limited salt water intake was included as a second control because the denervated rats consumed less salt than the controls. Plasma VP, OT and osmolality and posterior pituitary peptide content were measured. Brains were processed for evaluation of VP and OT mRNA expression using in situ hybridization with computer quantitation. Salt loading produced equivalent increases in plasma VP and OT in the control and SAD groups, however, there was a greater depletion of posterior pituitary peptides in the denervated animals. Salt loading produced significant decreases in pituitary VP and OT in the SAD animals, 69.8 +/- 8.4% and 68.3 +/- 4.0%, respectively. In the control groups, there was no decrease in VP content and a decrease in OT only in the control ad lib group. The peptide mRNA response to salt loading was also altered in the denervated rats. There was a significant increase in the area and intensity of the labeling for OT mRNA in the PVN in the SAD salt group. The control salt rats showed an increase in the SON and the salt-limited group showed no changes. For VP mRNA, the only change noted was in the SON of the salt-loaded SAD animals. These results show that chronic denervation of arterial baroreceptors augments the hypothalamic VP and OT response to salt loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of oxytocin on sodium excretion in the anaesthetized Brattleboro rat

The contribution of oxytocin to the maintenance of renal Na+ excretion in the Brattleboro rat has been examined in animals infused with hypotonic saline. Brattleboro rats exhibited hypernatraemia and hyperosmolality associated with greatly increased plasma concentrations of oxytocin by comparison with Long-Evans control rats. Neurohypophysectomy to remove the secretion of the remaining posterior pituitary peptide, oxytocin, led to greatly diminished rates of Na+ excretion in the Brattleboro rat. Oxytocin replacement to achieve plasma levels equivalent to those in intact Brattleboro rats produced a substantial and sustained natriuresis in the neurohypophysectomized animal. Oxytocin secretion evoked in response to saline infusion would thus appear to be effective in promoting renal Na+ excretion in the absence of vasopressin in the Brattleboro rat.

Which depressed patients will respond to electroconvulsive therapy? The search for biological predictors of recovery.

A small yet significant minority of contemporary patients with endogenous depressive illness who are treated with electroconvulsive therapy (ECT) gain little or no benefit. It is argued that the use of clinical features alone may not improve the ability to predict outcome after ECT. Many biological measures have been used to attempt to identify depressed patients for whom ECT would be an effective treatment, but none has yet been shown to be superior to clinical predictors. Depressed patients show a wide range of physiological responses to the first treatment of a course of ECT. Of these physiological responses, estimations of seizure threshold and of the release of posterior pituitary peptides merit further investigation as putative predictors of recovery.

Human platelet arginine vasopressin.

Approximately 90% of arginine vasopressin circulating in blood is associated with the platelets. Studies in six patients with cranial diabetes insipidus indicate that the platelet vasopressin originates in the hypothalamus and is taken up from plasma. Extracted platelet vasopressin is chromatographically identical to the posterior pituitary peptide and biologically active. Infusion of low-doses of exogenous vasopressin into 10 normal male subjects caused a marked rise in both plasma and platelet hormone concentrations. Stimulation of endogenous vasopressin release by hypertonic saline (0.51 mol/l) infusion for 135 min in five male subjects also caused a rise in platelet and plasma peptide concentrations. In seven male smokers, the deep inhalation of two consecutively smoked unfiltered cigarettes caused a significant rise in both platelet and plasma vasopressin. Baseline platelet vasopressin concentrations in the smokers were higher than in the non-smoking males even after 10 hours abstinence.

Influence of endogenous and exogenous oestrogens on posterior pituitary secretion in women.

Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d.

Posterior pituitary peptides in human foetal and neonatal tissues

Posterior pituitary peptides in human foetal and neonatal tissues

Vasopressin and central integrative processes.

Anatomical studies have suggested that the posterior pituitary peptide, vasopressin (VP, antidiuretic hormone) may be released at central neural sites other than the neurohypophysis. Immunohistochemical techniques allow VP to be visualized at numerous sites in the central nervous system (CNS). VP can also be measured in cerebrospinal fluid (CSF). Some of the stimuli which evoke VP release from the posterior pituitary may also elevate CSF VP levels. VP may play an important part in a variety of CNS functions. Substantial evidence exists implicating VP in learning and memory processes. VP may have a role in cardiovascular regulation through central pathways. Further, VP appears to act on the regulation of body temperature during fever. Other areas of central regulation where VP may be important include circadian rhythmicity, control of water intake, control of permeability of brain capillaries to water, central regulation of ACTH release and nociception. It appears that at least some of these central effects of VP involve an interaction with catecholaminergic neurotransmission.

Excitation of Hippocampal Neurones by Posterior Pituitary Peptides: Vasopressin and Oxytocin Compared

Publisher Summary Vasopressin and oxytocin can excite the mammalian neurons in brain slices in vitro . This chapter describes and systematically compares the potencies of oxytocin and vasopressin toward excitation of hippocampal neurons. The view that oxytocin and vasopressin might exert neurotransmitter-like actions in these areas is supported by the observation that these peptides can influence the rate of firing of single neurons when applied iontophoretically. Vasopressin readily and reproducibly excites a class of spontaneously active hippocampal neurons, which tends to fire in short intermittent bursts, and oxytocin also excites these neurons. However, oxytocin produces a much quicker and stronger effect than vasopressin. The experiment suggests that oxytocin is at least 10 times more powerful than arginine-vasopressin in the hippocampal slice. In another group of experiments, wherein, both arginine-vasopressin and oxytocin are applied, the hippocampal excitatory response seems purely oxytocic, because the effect of vasopressin can be entirely ascribed to its action on the postulated oxytocin receptors. Centrally acting neurohypophysial hormones can induce or modulate various behaviors. Oxytocin, however, may be equally important within the central nervous system, as oxytocin is found in many areas throughout the brain and spinal cord and has been shown to modulate the rate of firing of neurons located in the hypothalamus, brainstem, and spinal cord. Further studies are required to ascertain whether the postulated hippocampal oxytocin receptors resemble the known uterotonic or galactobolic oxytocin receptors in structure–activity requirements.

Estrogen-concentrating neurophysin-containing hypothalamic magnocellular neurons in the vasopressin-deficient (Brattleboro) rat: a study combining steroid autoradiography and immunocytochemistry

This report describes the distribution of neurophysin-containing, estradiol-concentrating neurons in a strain of rat which is congenitally unable to produce vasopressin and its associated neurophysin (the Brattleboro rat). In this strain of rat, all of the neurophysin-containing cells are oxytocin producing. The magnocellular neurons which produce vasopressin in the normal rat are present in their normal numbers and normal locations (Rhodes, C. H., J. I. Morrell, and D. W. Pfaff (1981) J. Comp. Neurol. 198: 45-64) and can be identified as the neurophysin-negative magnocellular neurons. Estradiol-concentrating cell nuclei were observed in magnocellular neurons with neurophysincontaining cytoplasm as well as in magnocellular neurons lacking immunocytochemically detectable neurophysin. The majority of these neurons were found in the paraventricular nucleus (PVN), ventral and medial to its lateral subnucleus, and in the posterior subnucleus of the PVN. There were, in addition, many neurophysin-containing and neurophysin-lacking magnocellular neurons with nuclei which did not concentrate estradiol. Within the PVN, the majority of the neurophysinnegative, non-estradiol-concentrating neurons were in the lateral subnucleus, while the majority of the neurophysin-positive, non-estradiol-concentrating neurons were in the medial subnucleus. Comparison of the results of experiments using homozygous Brattleboro rats with the results of similar experiments using the (normal) parent strain Long-Evans rat suggests that, in the normal animals, there are both oxytocinand vasopressin-producing neurons which concentrate estradiol. Comparison of these observations with published descriptions of the anatomical distribution of neurons which project to the medulla or spinal cord suggests that many of the oxytocin.or vasopressin-containing, estrogen-concentrating neurons in the PVN send axons to regions regulating autonomic functions. Estrogen treatment is a stimulus for the release of oxytocin (Yamaguchi et al., 1979) and vasopressin (Skowsky et al., 1979). A decrease in immunocytochem’ This paper is dedicated to the Rev. Dr. Winthrop Brainerd, Rector of Christ’s Church, Baltimore, formerly Keeper of Books and Manuscripts of Her Majesty’s College of Heralds, and author of Codici Monastici Ethiopiani. We wish to thank IL A. Zimmerman for the anti-neurophysin antiserum used in this work. This work was supported in part by National Institutes of Health Grants HD 05751 and HD 16327. C. H. R. was the recipient of National Research Service Award 5T32GM07739. ’ Present address: Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104. ” To whom correspondence should be addressed at Rockefeller University, 1230 York Avenue, New York, NY 10021. ically identified oxytocin has been observed in the anterior commissural nucleus (ACN) in response to estrogen treatment (Rhodes et al., 1981c). It is not known whether other magnocellular cell groups also participate in the estrogen-stimulated increase in plasma oxytocin levels or where estrogen acts to produce this effect. The fall in pituitary oxytocin content during proestrus and estrus in normal cycling female rats observed by Crowley et al. (1978) suggests that physiological changes in ovarian steroid levels affect the release of posterior pituitary peptides. The combination of steroid autoradiography and immunocytochemistry has been used to identify neurophysin-containing, estradiol-concentrating neurons in the (normal) parent strain Long-Evans rat (Rhodes et al., 1981a). That work was done with a primary antiserum

Partial gene duplication and posterior pituitary peptide.

We have compiled the dipeptide frequencies in 100 known protein sequences. We suggest that dipeptides which occur with low frequencies can be used to locate proteins where partial gene duplication may have taken place. The 48 residue sequence of posterior pituitary peptide contains two Cys Trp pairs. The adjacent portions of the sequence are compatible with a partial gene duplication in the evolutionary history of posterior pituitary peptide.

Natriuretic effect of posterior pituitary neurophysin.

ABSTRACT Neurophysins are peptides which are present in the neurohypophysis in association with oxytocin and vasopressin. Two neurophysins, I and II, have been isolated from bovine posterior pituitary powder. Neurophysin I intravenously administered to hydropenic dogs caused a significant (p < 0.001) increase in sodium excretion from 2.3 ± 0.3 μEq/min to 17.3 ± 3.8 μEq/min (mean ± sem). The peak natriuretic response occurred 90–120 minutes after injection of a bolus of neurophysin. Proximal renal tubule recollection micropuncture showed the basal tubular fluid/plasma inulin ratio (TF/P) of 1.50 ± 0.14 decreased significantly (p < 0.05) to 1.22 ± 0.06 (mean ± sem), after injection of neurophysin I. The decreased TF/P indicated a decrease in the fractional sodium reabsorption in the proximal tubule. Neurophysin II caused no change in urinary excretion. A biochemically specific posterior pituitary peptide has been demonstrated to have natriuretic activity in the dog. At least part of this action is due to an...

Paper chromatography of small amounts of vasopressins and oxytocins.

IN work concerned with the composition and estimation of neurohypophysial hormones in the posterior pituitary, the hypothalamus and body fluids, it would be desirable to have a chromatographic procedure which permits the identification in and recovery of small amounts of the active peptides from impure extracts. It would also be useful to know whether the substituted synthetic oxytocins which have recently been prepared1 can be distinguished by a simple chromatographic method. Taylor2 separated oxytocin, and arginine- and lysine- vasopressin by ion-exchange chromatography on resin columns. He used du Vigneaud's highly purified peptides, and the smallest amounts applied were equivalent to 0.6 mgm. of this material. Benfey3 purified Stehle and Fraser's4 preparations of ox posterior pituitary hormones (200 U./mgm. pressor activity and 250 U./mgm. oxytocic activity) by paper chromatography using ninhydrin as the colour reagent. The smallest amounts of the hormone preparations used were 1 mgm. However, since only terminal amino-groups react with ninhydrin, it is obviously disadvantageous to use this reagent when attempting to visualize very small quantities of the posterior pituitary peptides. Rydon and Smith5 have shown that micrograms of peptides of all kinds, including cyclopeptides, can be detected by chlorination followed by spraying with a starch–potassium iodide solution. Reindel and Hoppe6 improved this procedure in two ways. First, before exposure to chlorine, they moistened the paper with a mixture of watery ethanol and acetone, which prevents background staining. Secondly, they treated the N-chloropeptides with a mixture of potassium iodide and either benzidine or o-tolidine in acetic acid and thereby increased the sensitivity of the method.