Neurophysiology of body fluid homeostasis

1. Oxytocin as well as vasopressin is released in rats following systemic osmotic stimulation. There is evidence that, in the rat, oxytocin is a natriuretic hormone. 2. Osmotically-induced activation of oxytocin and vasopressin cells and osmotically-induced hormone secretion are diminished by ablation of tissue in the region anterior and ventral to the third ventricle (AV3V region). 3. The nature and identity of the osmoreceptors subserving oxytocin and vasopressin release are discussed.     

Effects of interleukins on plasma arginine vasopressin and oxytocin levels in conscious, freely moving rats.

To elucidate whether interleukins are involved in vasopressin or oxytocin release during cytokine-related stressful conditions, we examined the effects of human interleukin-1 beta and interleukin-6 on plasma vasopressin and oxytocin levels in rats. Interleukin-1 beta administrated intravenously stimulated both the vasopressin and oxytocin secretion in dose-dependent manners. Neither hormone release was observed following interleukin-6 administration. Pretreatment with aspirin significantly attenuated the effects of interleukin-1 beta on both the vasopressin and oxytocin levels. SC-19220, a prostaglandin E2 receptor antagonist, did not affect the interleukin-1 beta-induced increase of plasma oxytocin levels, but almost completely abolished its effect on plasma vasopressin levels. These results suggest that under certain stressful conditions which accompany the stimulation of cytokine production, interleukin-1 is involved in the increase of plasma vasopressin and oxytocin levels and, moreover, different kinds of prostaglandins are suggested to participate in these interleukin-1-induced hormone release.     

Coexisting peptides in hypothalamic neuroendocrine systems: Some functional implications

1. Coexisting with oxytocin or vasopressin in the cell bodies and nerve terminals of the hypothalamic-neurohypophysial system are smaller amounts of other peptides. For a number of these "copeptides" there is strong evidence of corelease with the major magnocellular hormones. Guided by the location of their specific receptors we have studied the effects of three copeptides, dynorphin, cholecystokinin (CCK), and corticotropin releasing hormone (CRH), on the secretion of oxytocin and vasopressin from isolated rat neural lobe or neurointermediate lobe preparations in vitro. 2. Dynorphin is coreleased with vasopressin from neural lobe nerve terminals and acts on neural lobe kappa-opiate receptors to inhibit the electrically stimulated secretion of oxytocin. Naloxone augments oxytocin release from the neural lobe in a manner directly proportional to the amount of vasopressin (and presumably dynorphin) released. 3. Cholecystokinin, coreleased with oxytocin by neural lobe terminals, has been shown to have high-affinity receptors located in the NL and to stimulate secretion of both oxytocin and vasopressin. CCK's secretagogue effect was independent of electrical stimulation and extracellular Ca2+ and was blocked by an inhibitor of protein kinase C. 4. CRH, coreleased with OT from the neural lobe, has receptors in the intermediate lobe of the pituitary, but not in the neural lobe itself. CRH stimulates the secretion of oxytocin and vasopressin from combined neurointermediate lobes but not from isolated neural lobes. Intermediate lobe peptides, alpha and gamma melanocyte stimulating hormone, induced secretion of oxytocin and vasopressin from isolated neural lobes. Their effect was, like that of CCK, independent of electrical stimulation and extracellular Ca2+ and blocked by an inhibitor of protein kinase C. 5. Among the CRH-producing parvocellular neurons of the paraventricular nucleus, in the normal rat, approximately half also produce and store vasopressin. After removal of glucocorticoid influence by adrenalectomy, virtually all of the CRH neurons contain vasopressin. 6. The two subtypes of CRH neurosecretory cells found in the normal rat possess different topographical distributions in the paraventricular nucleus, suggesting the possibility of differential innervation. Stress selectively activates the vasopressin containing subpopulation of CRH neurons, indicating that there are separate channels of regulatory input controlling the two components of the parvocellular CRH neurosecretory system.     

Effects of oxytocin,vasopressin and vasotocin and their agonists on steroid secretion by bovine granulosa cells

The effects of oxytocin and vasopressin and their agonists on the secretion of progesterone and oestradiol-17β by bovine luteinised granulosa cells cultured in a serum-supplemented medium were analysed. The effects of oxytocin (OT), its long-acting agonist 2-0-methyl-tyrosin (deamino-karba)-oxytocin (DK-OT), arginine-8-vasopressin (AVP), 1-desamino-arginine-8-vasopressin (D-AVP, a vasopressin analogue with high antidiuretic and without vasopressor properties) and arginine-8-vasotocin (AVT) were investigated. It was found that OT and DK-OT had a stimulatory effect on progesterone release, while AVP, D-AVP and AVT had an inhibitory effect. All peptide hormones investigated significantly increased oestradiol-17β secretion. The results suggest the involvement of nonapeptide hormones of both oxytocin and vasopressin groups in the regulation of steroidogenesis by granulosa cells from bovine ovarian follicles.     

The effect of gradual changes in temperature on the release of hormones from nerve endings isolated from bovine neural lobes.

Abstract— Homogenates of bovine neural lobe tissue were fractionated by differential centrifugation at 20°C or at 4°C and the distribution of activities of vasopressin and oxytocin among the fractions was compared. The ratio of total hormone to protein (mg) in the homogenate was similar at the two temperatures. At 20°C a much smaller proportion of the total hormone was recovered in the soluble fraction (100,000 g_av supernatant), than at 4°C with a corresponding increase in recovery in the nerve-ending fraction (800–3000 g sediment). Nerve endings isolated at 4°C did not, when incubated, release hormone in response to changes in temperature. Nerve endings isolated at 20°C released hormone when the temperature was reduced below 15°C. Gradual reduction in temperature led to hormone release unaccompanied by lactate dehydrogenase release. Incubation of nerve endings for 10 min at 10°C increased the release of vasopressin and of neurophysin without any increase in lactate dehydrogenase. These results demonstrate that release of vasopressin by cold stimulation occurs by way of exocytosis.     

Endocrine actions of opioids

The widespread occurrence of opioid peptides and their receptors in brain and periphery correlates with a variety of actions elicited by opioid agonists and antagonists on hormone secretion. Opioid actions on pituitary and pancreatic peptides are summarized in Table 1. In rats opioids stimulate ACTH and corticosterone secretion while an inhibition of ACTH and cortisol levels was observed in man. In both species, naloxone, an opiate antagonist, stimulates the release of ACTH suggesting a tonic suppression by endogenous opioids. In rats, a different stimulatory pathway must be assumed through which opiates can stimulate secretion of ACTH. Both types of action are probably mediated within the hypothalamus. LH is decreased by opioid agonists in many adult species while opiate antagonists elicit stimulatory effects, both apparently by modulating LHRH release. A tonic, and in females, a cyclic opioid control appears to participate in the regulation of gonadotropin secretion. Exogenous opiates potently stimulate PRL and GH secretion in many species. Opiate antagonists did not affect PRL or GH levels indicating absence of opioid control under basal conditions, while a decrease of both hormones by antagonists was seen after stimulation in particular situations. In rats, opiate antagonists decreased basal and stress-induced secretion of PRL. Data regarding TSH are quite contradictory. Both inhibitory and stimulatory effects have been described. Oxytocin and vasopressin release were inhibited by opioids at the posterior pituitary level. There is good evidence for an opioid inhibition of suckling-induced oxytocin release. Opioids also seem to play a role in the regulation of vasopressin under some conditions of water balance. The pancreatic hormones insulin and glucagon are elevated by opioids apparently by an action at the islet cells. Somatostatin, on the contrary, was inhibited. An effect of naloxone on pancreatic hormone release was observed after meals which contain opiate active substance. Whether opioids play a physiologic role in glucose homeostasis remains to be elucidated.     

Metabolic regulation by alpha 1- and alpha 2-adrenoceptors.

The role of alpha-adrenoceptors in the mediation of autonomic function, particularly in the control of the cardiovascular system, is widely known. However, alpha-adrenoceptors are also important in the regulation of a variety of metabolic processes that occur in the body either through direct action or by stimulation of the release of other mediators that control metabolic function. Thus, alpha 2-adrenoceptor activation by circulating or neuronally released catecholamines inhibits the release of insulin from pancreatic islet beta-cells and, by inhibiting this response, alpha 2-adrenoceptor antagonists have been shown to have an antihyperglycemic effect. The alpha-adrenoceptor-mediated regulation of the release of pituitary hormones is indirect, with alpha-adrenoceptors being located on peptidergic neurons in the hypothalamus that secrete releasing hormones into the hypophysial portal system to regulate the secretion of hormones from the anterior pituitary gland. Thus, the increase in cortisol secretion from the adrenal glands following a meal is produced, at least in part, by an alpha 1-adrenoceptor-mediated increase in vasopressin and CRF-41 secretion from neurons on the hypothalamus that stimulate the release of adrenocorticotrophic hormone secretion from the pituitary gland, which subsequently stimulates the synthesis and release of cortisol from the adrenal medulla. In addition to metabolic regulation by alpha 1- and alpha 2-adrenoceptors within the endocrine system, alpha-adrenoceptors are also a component of the system that regulates certain aspects of metabolism within autonomic effector cells, such as the control of smooth muscle cell division and growth during periods of continued alpha-adrenoceptor activation as a result of activation of second messenger systems.     

Rapid stimulation by vasopressin, oxytocin and angiotensin II of glycogen degradation in hepatocyte suspensions

1. The hormonal control of glycogen breakdown was studied in hepatocytes isolated from livers of fed rats. 2. Glucose release was stimulated by [8-arginine]vasopressin (10pm–10nm), oxytocin (1nm–1μm), and angiotensin II (1nm–0.1μm). These responses are all at least as sensitive to hormone as is glucose output in the perfused rat liver. 3. The effect of these three hormones on glucose release was critically dependent on extracellular Ca²⁺, unlike that of glucagon. Half-maximal restoration of the vasopressin response occurred if 0.3mm-Ca²⁺ was added back to the incubation medium. 4. Glycogen breakdown was more than sufficient to account for the glucose released into the medium, in the absence or presence of hormones. Lactate release by hepatocytes was not affected by vasopressin, but was inhibited by glucagon. 5. If Ca²⁺ was omitted from the extracellular medium, vasopressin stimulated glycogenolysis, but not glucose release. 6. The phosphorylase a content of hepatocytes was increased by vasopressin, oxytocin and angiotensin II; minimum effective concentrations were 0.1pm, 0.1nm and 10pm respectively. This response was also dependent on Ca²⁺. 7. These results demonstrate that hepatocytes can respond to low concentrations of vasopressin and angiotensin II, i.e. these effects are likely to be relevant in the intact animal. The role of extracellular Ca²⁺ in the effects of these hormones on hepatic glycogenolysis and glucose release is discussed.     

Inhibition of the permeability response to vasopressin and oxytocin in the toad bladder: Effects of bradykinin,kallidin, eledoisin,and physalaemin

Summary It has been shown by means of Bentley'sin vitro preparation of the isolated urinary bladder of the toad,Bufo marinus paracnemis Lutz, that bradykinin reversibly inhibited the increase brought about by vasopressin on the permeability to water of the toad bladder. The increased hydro-osmotic response of the bladder to oxytocin was also inhibited by the kinin. The effect on water permeability was observed when bradykinin was added either to the serosal Ringer's solution or to the mucosal solution. The addition of bradykinin alone did not alter the basal osmotic water transfer across the bladder. In this context, bradykinin acted as a competitive antagonist of vasopressin (and oxytocin). Although lacking intrinsic activity, bradykinin exhibited affinity for receptor sites that are also common to the neurohypophysial hormones, causing a parallel shift of the log-dose/response curve for vasopressin without changing the maximal responses. The effects of other kinins (namely kallidin, eledoisin and physalaemin) on the toad bladder were also tested. Each of these drugs alone did not change the basal water flux across the bladder wall. Like bradykinin, these peptides inhibited the increase in water permeability evoked by vasopressin and oxytocin in the bladder. In view of the importance of neurohypophysial hormones and their target tissues to the osmotic homeostasis of amphibians, and the observation of antagonism between the kinins and the pituitary hormones coupled to the abundance of kinins in the amphibian organism, particularly in the skin and urinary bladder, teleological reasoning predicts a physiological role for the kinins, possibly functioning to dampen excesses and oscillations in membrane permeability that could occur in face of a constant and variable secretion of neurohypophysial hormone, thus adding to the homeostatic response of the amphibian organism.     

Plasma galanin, vasopressin, and oxytocin in patients with Addison's disease.

Galanin is colocalized with adrenocorticotrophin (ACTH) in the human pituitary and with corticotrophin releasing hormone, arginine, vasopressin, and oxytocin in the hypothalamus. Galanin, vasopressin, and oxytocin influence the secretion of pituitary ACTH. The aim of this study was to investigate if the endogenous stimulation of ACTH release in Addison's disease was reflected in plasma galanin, vasopressin, and oxytocin. ACTH, galanin, vasopressin, and oxytocin were measured in plasma from 14 patients with Addison's disease, one patient with Nelson's syndrome, and 14 healthy controls. Eight patients had elevated plasma ACTH whereas six patients and all controls had ACTH levels within the reference-range. There was no difference in galanin or vasopressin between patients and controls or between samples with low or high ACTH concentrations. In contrast, oxytocin was higher in patients with elevated plasma ACTH compared to patients and controls with normal or low ACTH. No relation was found between galanin or oxytocin and age or sex. A tendency towards lower vasopressin with increasing age was found among the men (p=0.057). The highest ACTH and galanin levels were found in the patient with Nelson's syndrome. In conclusion, increased plasma ACTH was not reflected in elevated plasma galanin or vasopressin. In contrast, elevated ACTH levels were accompanied by higher oxytocin levels.     

Secretion of oxytocin and progesterone by ovine corpora lutea in vitro

The mechanisms involved in the control of oxytocin and progesterone secretion by the ovine corpus luteum have been investigated in vitro using luteal slice incubations. Oxytocin and progesterone were secreted at constant rates from luteal slices for 2 h of incubation (366 +/- 60 pg X mg X h and 18.9 +/- 0.18 ng X mg X h, respectively). Secretion of progesterone, but not of oxytocin, was significantly (p less than 0.02) stimulated in the presence of ovine luteinizing hormone. Incubation of luteal slices in medium containing 100 mM potassium, however, resulted in increased secretion of oxytocin and, to a lesser extent, of progesterone (294 +/- 59% and 142 +/- 15%, respectively, p less than 0.05). Basal oxytocin secretion was reduced during incubation in calcium-free medium, compared to secretion in the presence of calcium (70 +/- 15 and 175 +/- 25 pg X mg X 20 min, respectively, p less than 0.01), whereas progesterone secretion was not altered in the absence of calcium. Secretion of both hormones by luteal slices was stimulated by the addition of the calcium ionophore A23187 (p less than 0.05). Addition of prostaglandin F2 alpha (2.8 microM) had no effect on secretion of either oxytocin or progesterone. We have demonstrated that oxytocin and progesterone can be stimulated, independently, from corpus luteum slices incubated in vitro. The pattern of release is consistent with the proposal that oxytocin, but not progesterone, is associated with and actively released from luteal secretory granules. Our results also indicated that prostaglandin F2 alpha does not directly stimulate release of oxytocin or progesterone from luteal cells in vitro.     

Structure, processing and evolution of the neurohypophysial hormone-neurophysin precursors

Neurohypophysial hormones and neurophysins are derived from common precursors processed during the axonal transport from the hypothalamus to the neurohypophysis. Two neurohormones, an oxytocin-like and a vasopressin-like, on one hand, two neurophysins, termed VLDV-and MSEL-neurophysins according to residues in positions 2, 3, 6 and 7, on the other, are usually found in vertebrate species. In contrast to placental mammals that have oxytocin and arginine vasopressin, marsupials have undergone a peculiar evolution. Two pressor peptides, lysipressin and vasopressin for American species, lysipressin and phenylpressin for Australian macropods, have been identified in individual glands and it is assumed that the primordial vasopressin gene has been duplicated in these lineages. On the other hand, the reptilian mesotocin is still present in Australian species instead of the mammalian oxytocin, while the North American opossum has both hormones and South American opossums have only oxytocin. The neurophysin domain of each precursor is encoded by 3 exons and different evolutionary rates have been found for the 3 corresponding parts of the protein. The central parts, encoded by the central exons, are evolutionarily very stable and nearly identical in the 2 neurophysins of a given species. Recurrent gene conversions have apparently linked the evolutions of the 2 precursor lineages. In mammals, the 3-domain precursor of vasopressin is processed in 2 stages: a first cleavage splitting off vasopressin and a second cleavage separating MSEL-neurophysin from copeptin. Two distinct enzymatic systems seem to be involved in these cleavages. Processing is usually complete at the level of the neurohypophysis, but an intermediate precursor encompassing MSEL -neurophysin and copeptin linked by an arginine residue has been characterized in guinea pig. In vitro processing of this intermediate through trypsin--Sepharose reveals cleavages only in the interdomain region. In non-mammalian tetrapods, such as birds and amphibians, mesotocin and vasotocin are associated with neurophysins in precursors similar to those found in mammals. However, processing of the vasotocin precursor seems to be different from the processing of the vasopressin precursor, with a single cleavage leading to the hormone release.     

Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species.

The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the "Post-Proline Cleaving Enzyme", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.     

Peptides interact in gonadotrophin regulation

The regulation of luteinizing hormone (LH) activity is vital to normal reproductive functioning of the female. Although gonadotrophin-releasing hormone (GnRH) has a prominent role in the regulation of LH it is now believed that other peptides are also involved. Among these peptides is oxytocin. The addition of oxytocin to cultures of pituitary cells from female rats elicited a concentration-dependent secretion of LH. This secretion was enhanced in an oestrogenised environment and was inhibited by progesterone and testosterone. Oxytocin administered to female rats at pro-oestrus advanced the endogenous LH surge that occurs on the evening of pro-oestrus. Conversely oxytocin receptor antagonist suppressed the production of the LH surge in a dose-dependent manner, indicating that endogenous oxytocin is a crucial component of LH regulation. In the human female, oxytocin administered during the late follicular phase advanced the onset of the midcycle LH surge. Oxytocin added to rat pituitary cells in vitro induced LH synthesis. Furthermore rats administered oxytocin on pro-oestrus had higher LH pituitary content following development of the LH surge than did rats administered saline. Thus oxytocin promoted synthesis and replacement in the pituitary of LH released into the circulation. Incubation of pituitary pieces with oxytocin plus GnRH induced secretion of amounts of LH greater than the sum of the amounts released by oxytocin and GnRH separately. Additionally the increased LH levels observed in the peripheral circulation of pentobarbitone-anaesthetised rats administered GnRH were enhanced if the rats received oxytocin prior to the GnRH. Thus oxytocin synergised with GnRH in stimulating LH release. Addition of diBucAMP reduced the oxytocin-mediated augmentation and dideoxyadenosine enhanced the augmentation, suggesting that oxytocin worked most efficiently in a milieu low in cAMP activity. The use of a cell immunoblot assay revealed that individual cells responded differently to oxytocin and to GnRH and that the two peptides could act on the same cell. Perifusion studies performed on hemipituitaries demonstrated that a LH response could be determined by the presence of three peptides, oxytocin, neuropeptide Y and GnRH. Hence oxytocin is potentially involved also in multiple interactions during the process of LH regulation. LH regulation is therefore apparently the result of a community of peptides acting in a co-operative network.     

Effect of a prostacyclin analogue on the vasopressin and oxytocin secretion in vitro.

Iloprost (ZK 36374; a stable prostacyclin analogue) increases basal as well as potassium-evoked vasopressin and oxytocin secretion from rat neurointermediate lobes in vitro. This finding suggests a possible regulatory role of endogenous prostacyclin in the release of neurohypophysial hormones.     

Influence of peptides on 3H-dopamine release from superfused rat striatal slices

The effects of nine neuropeptides on the uptake and release of ³H-dopamine (DA) were studied in slices of rat striatum. Superfusion of preloaded slices at room temperature gave a steady release of ³H-DA after 30 min. Repetitive depolarisation with 20 mM K⁺ evoked pronounced, calcium-dependent releases of ³H-DA which declined exponentially. Substance P (SP), neurotensin and somatostatin all actively released ³H-DA, whilst cholecystokinin octapeptide (CCK), luteinising hormone releasing hormone (LHRH), thyrotrophin releasing hormone (TRH), adrenocorticotrophin (ACTH), vasopressin and oxytocin were without effect on spontaneous ³H-DA efflux. The effects of the peptides on K⁺-induced ³H-DA overflow were more varied; neurotensin, TRH and ACTH had no effect, whereas CCK, somatostatin and LHRH potentiated and SP, vasopressin and oxytocin attenuated ³H-DA release. None of the peptides altered the uptake of ³H-DA at the concentrations which modified its release (0.1–10 μM). It is suggested that modulating DA release may be fundamental to the central actions of these substances in the intact animal.     

The effects of chronic environmental stress on parturition and on oxytocin and vasopressin secretion in the pig

Previous work has suggested that an acute behavioural confinement in mid-partum can inhibit oxytocin secretion and prolong delivery in the pig, an effect that is opioid mediated. The present experiment investigated the effect of longer-term (chronic) behavioural confinement, that has previously been shown to elevate total plasma cortisol, on speed of delivery and on plasma oxytocin and lysine vasopressin concentrations during the peri-parturient period in primiparous pigs (gilts). Five days before their expected parturition (farrowing) date, gilts with preplaced jugular catheters were either confined to farrowing crates that severely restricted maternal behaviour, or housed in pens that permitted free movement and maternal behaviour (e.g. nest building). Blood samples were taken continuously from 24 h before the birth of the first piglet (BFP) to 6 h post-BFP, and for oxytocin on Days 1, 2, and 7 following parturition (Days P1, P2, P7). Both oxytocin and vasopressin were strongly influenced by parturition (P<0.001). There was no overall effect of chronic crating on either hormone, but crated and penned gilts did show significant differences with respect to the pattern of both oxytocin and vasopressin concentrations over time (P<0.05 in both cases). Oxytocin and vasopressin first increased in crated and penned gilts from 3 h pre-BFP (P<0.05). Crated gilts subsequently showed greater increases in both oxytocin and vasopressin over the first hour of delivery than penned gilts (mean oxytocin (pmol 1⁻¹): 53.3±8.5 vs. 39.7±5.0 for crated vs. penned gilts; mean vasopressin (pmol l⁻¹):4.4±0.7 vs. 2.0±04 for crated vs. penned gilts; both P<0.05). For oxytocin, crated gilts then showed subsequent declining concentrations relative to penned gilts (P<0.05). For vasopressin, penned gilts reached similar concentrations as crated gilts in the third hour post-BFP before vasopressin concentrations in both groups declined. Crated gilts also gave birth to piglets faster in the early stages of delivery (e.g. mean interval between Piglets 2 and 3 (min): 9.6±2.5 vs. 25.6±8.54 for crated and penned gilts, respectively: P<0.02). We conclude that confinement of gilts to a farrowing crate for 5 days neither adversely affects the progress of delivery in the primiparous pig nor the secretion of posterior pituitary hormones involved in parturition.     

Isolated mouse islets respond to glucose with an initial peak of glucagon release followed by pulses of insulin and somatostatin in antisynchrony with glucagon

Recent studies of isolated human islets have shown that glucose induces hormone release with repetitive pulses of insulin and somatostatin in antisynchrony with those of glucagon. Since the mouse is the most important animal model we studied the temporal relation between hormones released from mouse islets. Batches of 5-10 islets were perifused and the hormones measured with radioimmunoassay in 30s fractions. At 3mM glucose, hormone secretion was stable with no detectable pulses of glucagon, insulin or somatostatin. Increase of glucose to 20mM resulted in an early secretory phase with a glucagon peak followed by peaks of insulin and somatostatin. Subsequent hormone secretion was pulsatile with a periodicity of 5min. Cross-correlation analyses showed that the glucagon pulses were antisynchronous to those of insulin and somatostatin. In contrast to the marked stimulation of insulin and somatostatin secretion, the pulsatility resulted in inhibition of overall glucagon release. The cytoarchitecture of mouse islets differs from that of human islets, which may affect the interactions between the hormone-producing cells. Although indicating that paracrine regulation is important for the characteristic patterns of pulsatile hormone secretion, the mouse data mimic those of human islets with more than 20-fold variations of the insulin/glucagon ratio. The data indicate that the mouse serves as an appropriate animal model for studying the temporal relation between the islet hormones controlling glucose production in the liver.     

Isolation and localization of neurophysin-like proteins in rat uterus

Neurophysins are part of the prohormones for vasopressin and oxytocin, and are localized with these hormones in the magnocellular cells of the neurohypophysis. New techniques have identified neurophysins in other areas within and outside the central nervous system, and we report here the isolation of neurophysins from the uterus of the rat. Using immunohistology the neurophysin immunoreactivity was localized to the epithelial lining cells of the uterus, and using radioimmunoassay was also present in uterine fluid suggesting secretion into the uterine cavity. The amount of uterine neurophysin increased in response to administered estrogen and was especially elevated in the pregnant uterus. The neurophysin-like material isolated from the uterus was similar to neurophysins from the neurohypophysis by radioimmunoassay, molecular sieve chromatography, isoelectric focusing and SDS gel electrophoresis. Both neurohypophyseal hormones, vasopressin and oxytocin, were also extracted from uterine endothelium and identified by radioimmunoassay and high pressure liquid chromatography.     

Selective serotonin reuptake inhibitors and neuroendocrine function.

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.