Release Of Posterior Pituitary Hormones Research Articles

Role of Midbrain Parabrachial Nucleus in Controlling Electrical Activity of Oxytocin and Vasopressin Secreting Neurones in the Hypothalamic Supraoptic Nucleus.

Release of posterior pituitary hormones is known to be controlled by hemodynamic information in addition to factors related to reproductive function such as suckling stimulus by pups during lactation and afferents from the uterine cervix during parturition. The midbrain parabrachial nucleus, which is one of the major sites for the integration of the autonomic function, sends heavy projections to the hypothalamic supraoptic and paraventricular nuclei which contain oxytocin and vasopressin secreting neurones. The present experiments were undertaken to examine the physiological role of these projections. Electrical stimulation of the parabrachial nucleus increased the excitability of 65% of putative oxytocin neurones, and 60% of putative vasopressin neurones. Electrolytic lesion of the parabrachial nucleus itself did not affect the basal firing rate, which suggests that inputs from the parabrachial nucleus to the supraoptic nucleus are not tonically driven. Although the lesion did not change the responsiveness of neurones to hyperosmotic stimulation, it affected the responsiveness of putative vasopressin neurones to the decrease of blood pressure. In addition to the well-known role of neurosecretory neurones in reproductive functions, these neurones may change their electrical activity in response to inputs driven by the parabrachial nucleus and contribute to the control of body fluid balance.

Expression of Angiotensin Type-1 (AT1) and Type-2 (AT2) Receptor mRNAs in the Adult Rat Brain: A Functional Neuroanatomical Review

The discovery that all components of the renin–angiotensin system (RAS) are present in the central nervous system led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood–brain barrier deficient circumventricular organs are rich in angiotensin II receptors. By activating these receptors, circulating angiotensin II may act on central cardiovascular centers via angiotensinergic neurons, providing a link between peripheral and central angiotensin II systems. Among the effector peptides of the brain RAS, angiotensin II and angiotensin III have the same affinity for the two pharmacologically well-defined receptors: type 1 (AT1) and type 2 (AT2). When injected in the brain, these peptides increase blood pressure, water intake, and anterior and posterior pituitary hormone release and may modify memory and learning. The cloning of AT1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated. Using specific riboprobes forin situhybridization histochemistry, recent studies mapped the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the brain and of AT1B in the pituitary. Very limited overlap was found between the brain expression of AT1A and AT2 mRNAs. In several functional entities of the brain, such as the preoptic region, the hypothalamus, the olivocerebellary system, and the brainstem baroreflex arc, the colocalization of receptor mRNA, binding sites, and angiotensin immunoreactive nerve terminals suggests local synthesis and expression of angiotensin II receptors. In other areas, such as the bed nucleus of the stria terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic origin. The neuronal expression of AT1A and AT2 receptors was demonstrated in the subfornical organ, the hypothalamus, and the lateral septum. By using double labelin situhybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus. The information is discussed together with functional data concerning the role of brain angiotensins, in an attempt to provide a better understanding of the physiological and functional roles of each receptor subtype.

Interrelated adrenocortical and neurohypophysial responses associated with fever in endotoxin-treated pigs.

Low intravenous doses of endotoxin [lipopolysaccharide (LPS), 0.7 microgram/kg] induce monophasic fever, increase anterior and posterior pituitary hormone release, and enhance hypothalamic c-Fos expression in pigs, all of which can be prevented by indomethacin (Ind). The present study shows that the synthetic corticosteroid dexamethasone (Dex, 5 mg/kg) has a similar action to Ind and, when given alone, lowers core temperature. In addition, the corticosteroid synthesis inhibitor metyrapone (Met, 3.3 mg/kg, every one-half hour) reduces LPS fever and amplifies the effect of LPS on vasopressin, but not on oxytocin, release. The similar actions of Dex and Ind suggest that phospholipase A2 pathways controlling prostaglandin synthesis mediate the responses of prepubertal pigs to immunological challenge with LPS. The increased vasopressin release induced when animals receiving Met are also given LPS supports findings in other nonrodent species indicating an inverse relationship between cortisol and vasopressin. The attenuation of LPS fever by Met is suggestive of an endogenous antipyretic mechanism associated with enhanced neurohypophysial vasopressin secretion.

Neuroendocrine response during stress with relation to gender differences.

Neuroendocrine activation belongs to the main characteristics of the stress response. This response is not uniform but depends on the stress stimulus involved and on many other factors including the gender of the individual. In rats, corticosterone and ACTH levels as well as functional activity of the hypothalamo-pituitary-adrenocortical axis are higher in females compared to males under both basal and stress conditions. Marked sex differences were observed in stress-induced changes posterior pituitary hormone release. In male rats, release of vasopressin is not stimulated during stress conditions without an osmotic component while in female rats a rise in plasma vasopressin levels was observed even after short immobilization. Oxytocin release is enhanced in response to the majority of stress stimuli and it was found to be greater in females than in males. Mentioned gender differences are attributed to the effect of sex steroids, particularly those of estrogens. Not enough information is available on gender differences in the neuroendocrine response during stress in humans. We observed a greater neuroendocrine activation in women than in men in response to heat exposure in sauna with pronounced differences in ACTH and prolactin release and partly also after a cold-pressor test. Understanding of gender differences in neuroendocrine response during stress might contribute to the explanation of the development of some emotional and other disorders with higher incidence in women.

Vasopressin and oxytocin in stress.

Though oxytocin and vasopressin are similar in structure and are produced in the same brain regions, they show specific responses under stress conditions. In humans, increases in peripheral blood vasopressin appear to be a consistent finding during many acute stress situations, while in rats, vasopressin secretion is unresponsive to several stimuli known to induce ACTH and catecholamine release. Even decreases in vasopressin levels during stress were described. In accordance with others, we observed enhanced vasopressin release in response to stress stimuli with an osmotic component such as hypertonic saline injection but also during exposure of rats to a warm environment. Immobilization stress which fails to induce vasopressin release was reported to increase hypothalamic vasopressin mRNA and plasma vasopressin levels in chronically adreno-demedullated rats. Unlike vasopressin, oxytocin may be considered a typical stress hormone responding to osmotic as well as other stress stimuli. We found that acute exposure of rats to immobilization stress resulted in an increase in oxytocin mRNA level. In addition, we have shown that magnocellular neurons of the paraventricular nucleus, but not the supraoptic nucleus, are essential for oxytocin release during immobilization stress. The release of posterior pituitary hormones represents an important component of the stress response.

Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig

Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but no change in adrenaline or noradrenaline levels was observed. All these effects were prevented or attenuated when the animals were pretreated intravenously with the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal expression of c-Fos were observed in hypothalamic regions concerned with thermoregulation, neurohypophysial secretion, and the control of pituitary-adrenocortical function. The stimulatory action of LPS in the median preoptic, supraoptic and paraventricular nuclei was prevented by IND, whereas IND given alone was without effect. These findings suggest that inducible cyclo-oxygenase pathways are responsible for the febrile and neuroendocrine effects of endotoxin in this species.

Endothelin mechanisms in the central nervous system: A target for drug development

AbstractEndothelin (ET), a vasoconstrictor peptide, was isolated and characterized in 1988. Since then extensive studies have been done in different animal species to identify its receptors in central nervous system (CNS) and peripheral tissues. Three forms of ETs have been identified: ET‐1, ET‐2, and ET‐3. Their distribution pattern and pharmacological functions have been defined. ET‐1 and ET‐2 are mainly distributed in the CNS, including spinal cord and the peripheral tissues, while ET‐3 although present in other tissues is mainly concentrated in the pituitary. ET receptors have been found to be coupled to intracellular pathways involving stimulation of Ca++ fluxes, through phospholipase C and inhibition of adenyl cyclase. The literature concerning central actions of ET has been reviewed. The bulk of the evidence shows that it may be a regulator of regional cerebral blood flow, and a modulator of the release of posterior pituitary hormones (oxytocin and vasopressin). It may also regulate the release of prolactin, growth, thyroid stimulating, or luteinizing hormones. The regulatory role of ET on cardiovascular system can be exerted by central as well as peripheral actions. Besides direct regulation, ET modulates the release of endothelium derived relaxing factor/nitric oxide (EDRF/NO) and increases the sensitivity of peripheral α‐adreno‐ceptors. Thus ET appears to establish a balance between vasodilatation induced by EDRF/NO release and vasoconstriction due to increased sensitivity of vascular a‐adrenoceptors. The level of ET was found to be raised in several pathological conditions like subarachnoid hemorrhage, myocardial infarction, cardiogenic and septic shock, Raynaud's disease, and pulmonary hypertension. Its level was also raised in patients undergoing chronic hemodialysis. On the other hand, the level of ET was significantly lower in the cerebrospinal fluid (CSF) of patients of depression. The available data suggest that ET has a neuromodulatory role in the CNS and may be involved in the pathophysiological processes of several diseases. ET mechanisms in the CNS could provide potential targets for the development of newer drugs. © 1992 Wiley‐Liss, Inc.

Anterior and posterior pituitary hormone release induced in sheep by cholecystokinin.

The effect of an intravenous bolus injection of cholecystokinin octapeptide (CCK-8; 0.85 micrograms/kg) on the release of cortisol, prolactin, vasopressin, and oxytocin was studied in sheep (n = 10). Concentrations of these hormones were measured in blood samples taken before (-10, 0 min) and after (5, 10, 20 min) administration of a saline vehicle or vehicle + CCK. Following CCK treatment, levels of cortisol were raised after 10 and 20 min, prolactin and vasopressin concentrations were increased after 5 min, and oxytocin secretion was unaffected.

Adenosine interaction with adenylate cyclase in rat posterior pituitary

An adenosine-sensitive adenylate cyclase has been demonstrated in rat posterior pituitary in the present studies. N-Ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-Cl-Ado) and l- N 6-phenylisopropyladenosine (PIA) all stimulated adenylate cyclase in a concentration-dependent manner, with an apparent K a between 0.5 and 1 μM. NECA was most effective and stimulated adenylate cyclase by about 100%, whereas 2-Cl-Ado and PIA stimulated the enzyme activity by about 60%. The activation of adenylate cyclase by NECA was dependent on the concentrations of metal ions such as Mg 2+ or Mn 2+. The stimulatory effect of NECA on adenylate cyclase was completely blocked by 3-isobutyl-l-methylxanthine (IBMX) and 8-phenyltheophylline. Adenosine showed a biphasic effect on adenylate cyclase: stimulation at lower concentrations and inhibition at higher concentrations, whereas 2′-deoxyadenosine and 2′5′-dideoxyadenosine inhibited adenylate cyclase in a concentration-dependent manner. In addition, dopamine, isoproterenol and forskolin also stimulated adenylate cyclase to various degrees and the stimulatory effect of isoproterenol and forskolin was found to be additive with the stimulation exerted by NECA. These data indicate the presence of adenosine stimulatory receptors Ra/A 2 in posterior pituitary which are coupled to adenylate cyclase. It is possible that adenosine may act as one of the important regulators to regulate and/or modulate the release of posterior pituitary hormones

GABA receptor stimulation increases the release of vasopressin and oxytocin in vitro

The release of oxytocin and vasopressin from rat neurointermediate lobes was determined in vitro. The electrically evoked release of posterior pituitary hormones was markedly potentiated by the GABA receptor agonist, isogauvacin, an effect which was abolished by the GABA A receptor antagonist bicuculline. Spontaneous hormone outflow was not affected by the substances tested. The results suggest the existence of a GABA receptor on the terminal fibres in the pituitary, facilitating the release of oxytocin and vasopressin.

VASOACTIVE INTESTINAL PEPTIDE (VIP) STIMULATES OXYTOCIN AND VASOPRESSIN RELEASE FROM THE NEUROHYPOPHYIS

The concentration of vasoactive intestinal peptide (VIP) was measured by RIA in pituitary extracts of female cats; it was significantly higher in the posterior than in the anterior lobe, 47.3 +/- 3.9 pmol/g wet wt vs. 7.7 +/- 2.0 pmol/g wet wt (mean +/- SE, n = 5 in both instances). To investigate the effect of VIP on the release of posterior pituitary hormones, the concentration of arginine vasopressin and oxytocin was measured by RIA in jugular vein plasma during intracarotid infusion of VIP. The levels of both hormones rose during the 5-min infusion of VIP. Oxytocin levels increased from a mean of 7.9 microU/ml to a maximum of 34.9 microU/ml at 1 min and arginine vasopressin levels from from 27.4 microU/ml to a maximum of 157 microU/ml at 1 min. The levels of both hormones returned to baseline values in about 20 min. Since VIP has been localized to the nerve terminals of the neurohypophysis, these data suggest that endogenous VIP may play a role as a neurotransmitter in the magnocellular hypothalmo-neurosecretory system.

The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat.

AbstractAxonal transport techniques were used to define the organization of projections from the forebrain to the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus in the adult rat. First, injections of a retro‐gradely transported fluorescent tracer, true blue, were placed in the region of the PVH, and the distribution of retrogradely labeled cells was charted. Then, the autoradiographic method was used to confirm the results of the retrograde transport experiments, to describe the route taken by inputs to the PVH and SO, and to determine the distribution of each projection within the various subdivisions of the nuclei that have been recognized previously on the basis of cytoarchitectonics, efferent projections, and immunohisto‐chemistry.The results can be summarized as follows. First, direct projections to the PVH arise from all areas of the hypothalamus (except the SO, the medial and lateral mammillary nuclei, and the magnocellular preoptic nucleus), and from the subfornical organ and the bed nucleus of the stria terminalis. Second, every forebrain region projecting directly to the PVH appears to innervate cell groups in parvocellular parts of the nucleus that in turn project to the neurohemal zone of the median eminence, and to autonomic centers in the brainstem and spinal cord. In addition, each input has a unique distribution within the parvocellular division. Third, relatively few regions in the forebrain project directly to magnocellular neurosecretory parts of the PVH, and are thus in a position to influence directly the release of posterior pituitary hormones. These regions (each of which also projects to the parvocellular division) include the dorsomedial nucleus of the hypothalamus, the median preoptic nucleus, the subfornical organ, and the bed nucleus. Therefore, inputs from the hippocampal formation, amygdala, and lateral septum that have been shown to influence the magnocellular neurosecretory system appear to be relayed by way of short projections from other parts of the hypothalamus (including perhaps parvocellular parts of the PVH) and from the bed nucleus. Fourth, most of these cell groups innervate preferentially either oxytocinergic (dorsomedial and bed nuclei) or vasopressinergic (subfornical organ) parts of the magnocellular division of the PVH. Only the projection from the median preoptic nucleus appears to be distributed uniformly over parts of the magnocellular division in which oxytocin‐ and vasopressin‐con‐taining cells are concentrated. And fifth, each region that preferentially innervates either oxytocinergic or vasopressinergic neurons in the PVH also preferentially innervates the same cell type in the SO (which does not contain a distinct parvocellular division). The results indicate that the coordination of neuroendocrine and autonomic responses from the PVH is mediated at least in part by a complex series of neural inputs, each of which innervates more than one functional subdivision within the nucleus.

Adaptation of nitrogen metabolism to hyperosmotic environment in Amphibia

AbstractA large number of species of Amphibia, both Anura and Urodela, are capable of tolerating a moderately saline environment. Rana cancrivora, Bufo viridis, and Xenopus laevis are among the most euryhaline frogs so far studied. Rana cancrivora can tolerate undiluted seawater. In a saline environment, Amphibia show raised plasma sodium and chloride and raised intracellular potassium and chloride. In the adults, plasma and tissue urea are elevated, especially in the more euryhaline species. Free amino acids contribute negligibly to plasma osmolarity, but are very important in intracellular fluids. By these various means, the osmotic pressure of body fluids is always maintained at a higher level than that of the surroundings. Larval Amphibia, however, do not make urea; Rana cancrivora tadpoles can live in saltwater, but maintain the osmolarity of their body fluids below that of their surroundings.Adaptive responses to hyperosmolar environment include decreased skin sodium transport, greatly reduced urine flow, and release of posterior pituitary hormones. After the initial response, the release of these hormones declines, and urine flow increases. Accumulation of urea occurs slowly, but this substance plays an increasingly important role as adaptation proceeds. Accumulation is due initially to urea retention, and possibly to greater synthesis due to a high concentration of precursors of the urea cycle. In later stages of adaptation, increased urea synthesis is due to elevated levels of urea cycle enzymes, especially those that appear to have been rate‐limiting. Liver glutamate dehydrogenase is also elevated. In animals subjected to pure osmotic stress, in solutions not containing sodium, responses are similar to, but not identical with, those caused by a medium containing sodium chloride.

Synthesis, transport, and release of posterior pituitary hormones.

Vasopressin and oxytocin are made and released by neurons of the hypothalamo-neurohypophysial system. Pulse labeling these neurons with radioactive amino acid indicates that the two hormones and their respective neurophysin carrier proteins are synthesized as parts of separate precursor proteins. The precursors seem to be processed into smaller, biologically active molecules while they are being transported along the axon.

Release of posterior pituitary hormones from the entire hypothalamoneurohypophysial system in vitro

Release of posterior pituitary hormones from the entire hypothalamoneurohypophysial system in vitro

Evidence for a hypothalamic control of renal sodium excretion.

AbstractSlow infusions (7.5 μl/min) of hypertonic NaCl into the 3rd brain ventricle of goats maintained on a NaCl‐supplemented diet provoked natriuresis reaching maximum about 70 min after onset of the infusions. The natriuresis was less pronounced in animals receiving no dietary NaCl‐supplementation. The magnitude of the natriuretic response was dependent on the molarity of the NaCl infused and on infusion duration. A much smaller relative increase in K excretion, reaching peak values 20 min before maximum natriuresis, also occurred. Aldosterone treatment did not prevent the natriuretic response and it could be elicited in diabetes insipidus animals, showing that release of posterior pituitary hormones was not essential. Determinations of inulin clearance (CIn) indicated that glomerular filtration rat (GFR) increased and that relative reabsorption of Na+ decreased during the natriuresis.Similar intraventricular infusions of hypertonic NH4Cl resulted in greatly diminished renal Na+ excretion lasting for about 2 hrs. Such infusions also delayed by 90 min the normal natriuretic response to an intravenous NaCl load. CIn determinations indicated that a diminished GFR may have contributed to this reduction in renal Na+ excretion. The results indicate that renal Na+ excretion is under hypothalamic control in the goat. Possible mechanisms for this control are discussed.

Cholinesterase in the Diencephalon of the Hen in Relation to Egg Laying

THE involvement of a neural component in the mechanism of ovulation in the hen was demonstrated by the blockade of ovulation with adrenolytic and para-sympatholytic drugs (Zarrow and Bastian, 1953) or oviducal irritation (Huston and Nalbandov, 1953; van Tienhoven, 1953), and by the stimulation of ovulation with certain barbiturates (Fraps and Case, 1953). Fraps (1954) postulated that the neural component had a diurnal periodicity in the threshold level of excitation for discharge of LH to cause ovulation.Premature oviposition with a para-sympathomimetic drug (Weiss and Sturkie, 1952) or the irritation of uterus by a loop of thread (Sykes, 1953), and delayed oviposition with sympathomimetic drugs (Weiss and Sturkie, 1952; Sykes, 1955) suggest the involvement of nervous factors in the regulation of oviposition in the hen, although it remains undetermined whether the nervous factors act on the uterus directly or through the release of posterior pituitary hormones which in turn cause …

Loss of sodium from the skin of the dehydrated toad, Bufo marinus.

THE movement of sodium across the skin of frogs and toads has been studied extensively1. Bufo marinus placed in distilled water loses sodium from the skin at an increased rate when injected with large doses of ‘Pitressin’2. Increase in concentration of the body fluids as in dehydration potentiates posterior pituitary hormone release in mammals, and the same appears to be the case in amphibians3. Therefore it was of interest to see what effect such endogenous release of posterior pituitary hormone had on loss of sodium from the skin.