Neurohypophysial Hormones Associated with Osmotic Challenges in the Brain and Pituitary of the Euryhaline Black Porgy, Acanthopagrus schlegelii.

Our study showed differential expression of the arginine vasotocin (avt)/isotocin (it) in the brain and pituitary gland of the euryhaline black porgy (Acanthopagrus schlegelii) during osmotic stress. A decrease in serum osmolality and increased cortisol levels were observed after acute transfer from seawater (SW) to freshwater (FW). The increased expressions of avt, avt receptor (avtr: v1a), and isotocin receptor (itr: itr1) transcripts on day 1 and it and itr transcripts on days 7 and 30 were found in the brains and pituitary glands of FW fish. Increased levels of avt mRNA in the diencephalon and avtr mRNA in the pituitary together with serum cortisol on day 1 of FW exposure indicated activation of the hypothalamic-pituitary-interrenal (HPI) axis. The expression levels of avtr and itr after FW transfer were increased in the pituitary on days 7 and 30. Furthermore, in situ hybridization demonstrated spatially differential expression of avt and itr transcripts in nucleus preopticus parvocellularis of pars gigantocellularis (PMgc), magnocellularis (PMmc), and parvocellularis (PMpc) of the preoptic area (POA). Positive signals for avt and it were highly abundant in PMpc after FW exposure. The data suggest involvement of neurohypophysial hormones in the brain (telencephalon and diencephalon) and pituitary for osmotic stress.

Molecular mechanisms involved in the control of neurohypophyseal hormones secretion.

The regulation of neurohypophyseal peptides secretion reflects the convergence of a large number of afferent neural pathways on vasopressinergic and oxytocinergic neurons of supraoptic (SON) and paraventricular nuclei (PVN). In addition to afferent input, vasopressin and oxytocin can also exert an autocrine regulation of neuronal activity. In fact, magnocellular neurons (MCNs) of SON and PVN are able to secrete these hormones not only at the endings of their terminal axons, but also from their dendrites and this local release, by activating a range of ion gated, ion channel and G protein coupled receptors, participate in pre- and post-synaptic modulation of neural activity of MCNs. In this review we analyzed the molecular mechanisms involved in the control of neurohypophyseal hormones secretion and related possible pharmacological targets.

Endogenous angiotensin II-induced p44/42 mitogen-activated protein kinase activation mediates sodium appetite but not thirst or neurohypophysial secretion in male rats.

The renin-angiotensin-aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen-activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin-converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap-induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap- or exogenous AngII-induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII-induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed.

Membrane structure and interactions of peptide hormones with model lipid bilayers.

In this work, the behavior of the neurohypophyseal hormones and their selected analogs was studied in the presence of membrane models in an attempt to correlate their activities with a distinct behavior at a level of peptide-lipid interactions. The influence of the peptides studied on the lipid acyl chain order was determined using FTIR spectroscopy. Conformational changes in the peptides upon binding to liposomes were examined using CD spectra. Attempts were also made to determine the binding parameters of the peptides to lipids using isothermal titration calorimetry (ITC). The results show unambiguously that the neurohyphophyseal hormone-like peptides interact with lipids, being a model of a eukaryotic cell membrane. Moreover, hydrophobic interactions between the peptides and liposomes are likely to determine the overall conformation of the peptide, especially below the temperature of the main phase transition (T(m)). Thus, the bulky and hydrophobic nature of the residues incorporated into the N-terminal part of neurohyphophyseal hormones is an important factor for both restriction of peptide mobility and the interaction of the analog with biomembrane. In turn, above T(m), the electrostatic interactions become also relevant for the conformation of the acyclic tail of the AVP-like peptides.

The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors.

The neurohypophysial peptides of the vasopressin (VP) and oxytocin (OT) families regulate salt and water homeostasis and reproduction through distinct G protein-coupled receptors. The current thinking is that there are four neurohypophysial hormone receptors (V1aR, V1bR, V2R, and OTR) in vertebrates, and their evolutionary history is still debated. We report the identification of a fifth neurohypophysial hormone receptor (V2bR) from the holocephalan elephant fish. This receptor is similar to conventional V2R (V2aR) in sequence, but induced Ca(2+) signaling in response to vasotocin (VT), the non-mammalian VP ortholog; such signaling is typical of V1-type receptors. In addition, V1aR, V1bR and OTR were also isolated from the elephant fish. Further screening revealed that orthologous V2bRs are widely distributed throughout the jawed vertebrates, and that the V2bR family is subdivided into two subfamilies: the fish specific type-1, and a type-2 that is characteristically found in tetrapods. Analysis suggested that the mammalian V2bR may have lost its function. Based on molecular phylogenetic, synteny and functional analyses, we propose a new evolutionary history for the neurohypophysial hormone receptors in vertebrates as follows: the first duplication generated V1aR/V1bR/OTR and V2aR/V2bR lineages; after divergence from the V2bR lineage, the V2aRs evolved to use cAMP as a second messenger, while the V2bRs retained the original Ca(2+) signaling system. Future studies on the role of V2bR in the brain, heart, kidney and reproductive organs, in which it is highly expressed, will open a new research field in VP/VT physiology and evolution.

The relationship of appetitive, reproductive and posterior pituitary hormones to alcoholism and craving in humans.

A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormones are strongly associated with alcohol use. While medical consequences are important, the primary focus of this review is on the underlying confluence of appetitive/feeding, reproductive and posterior pituitary hormones associated with distinct phases of alcoholism or assessed by alcohol craving in humans. While these hormones are of diverse origin, the involvement with alcoholism by these hormone systems is unmistakable, and demonstrates the complexity of interactions with alcohol and the difficulty of successfully pursuing effective treatments. Whether alcohol associated changes in the activity of certain hormones are the result of alcohol use or are the result of an underlying predisposition for alcoholism, or a combination of both, is currently of great scientific interest. The evidence we present in this review suggests that appetitive hormones may be markers as they appear involved in alcohol dependence and craving, that reproductive hormones provide an example of the consequences of drinking and are affected by alcohol, and that posterior pituitary hormones have potential for being targets for treatment. A better understanding of the nature of these associations may contribute to diagnosing and more comprehensively treating alcoholism. Pharmacotherapies that take advantage of our new understanding of hormones, their receptors, or their potential relationship to craving may shed light on the treatment of this disorder.

Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of arginine vasopressin (AVP), an antidiuretic hormone. Although the carriers are normal at birth, polyuria and polydipsia appear several months or years later. Previously, we made mice possessing a mutation causing FNDI and reported that the mice manifested progressive polyuria as do the patients with FNDI. Here, we report that decreases in AVP mRNA expression in the supraoptic nucleus were accompanied by shortening of the AVP mRNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons. Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors (thapsigargin and tunicamycin) caused shortening of the poly(A) tail length of AVP and oxytocin mRNA, accompanied by decreases in their expression. On the other hand, an ER stress-reducing molecule (tauroursodeoxycholate) increased the poly(A) tail length as well as the expression levels of AVP and oxytocin mRNA. These data reveal a novel mechanism by which ER stress decreases poly(A) tail length of neurohypophysial hormones, probably to reduce the load of unfolded proteins.

Centrally administered ascorbic acid induces antidiuresis, natriuresis and neurohypophyseal hormone release in rats.

OBJECTIVE: Ascorbic acid represents one of the most important antioxidants and neuromodulators, and plays an important role in the cerebral system. In the present study, we investigated the central effect of ascorbic acid on fluid regulation and electrolyte homeostasis. METHODS: Male Wistar rats were implanted with stainless steel cannulas into the lateral ventricle, and sodiun excretion and urinary volume were measured after intracerebroventricular (i.c.v.) injection of ascorbic acid (200 or 600 nmol/rat). In another set of experiments, vasopressin and oxytocin plasma levels were evaluated 10, 20 and 30 minutes after ascorbic acid i.c.v. injection. RESULTS: The administration of ascorbic acid to conscious rats resulted in a significant decrease in urinary volume and an increase in the renal excretion of sodium, with a concomitant increase in the plasma levels of vasopressin and oxytocin. CONCLUSIONS: These results suggest that ascorbic acid may play a significant role in the central regulation of fluid and electrolyte homeostasis.

Love and attachment: the psychobiology of social bonding.

Basic animal studies and human imaging studies have contributed to our understanding of the psychobiology of love and attachment. There are overlaps and distinctions in the neuronal circuitry of maternal love, romantic love, and long-term attachment. In these circuits, important molecules, which have been demonstrated to play a role in the psychobiology of social bonding include dopamine, serotonin, opioids, oxytocin, and vasopressin. Particular genetic and environmental variations contribute to social-bonding phenotypes, consistent with an evolutionary perspective on the value of these behaviors. Advances in the psychobiology of social bonds have led to hypotheses about the pharmacotherapy of disorders of attachment.

Unique form and osmoregulatory function of a neurohypophysial hormone in a urochordate.

The cyclic nonapeptides, oxytocin and vasopressin, are neurohypophysial hormones that regulate many significant physiological processes related especially to reproduction and osmoregulation. In this study, we characterized an oxytocin-related peptide cDNA from a urochordate, Styela plicata, thought to be a sister group to vertebrates. Sequence analysis of the deduced precursor polypeptide revealed that the precursor is composed of three segments: a signal peptide, an oxytocin-like sequence flanked by a Gly C-terminal amidation signal and a Lys-Arg dibasic processing site, and a neurophysin domain, similar to other oxytocin/vasopressin family precursors. However, unlike other members of this family, the tunicate oxytocin-like peptide (CYISDCPNSRFWST-NH2) is a tetradecapeptide. We termed this peptide Styela oxytocin-related peptide (SOP). Furthermore, analyses of mass spectrometry, in situ hybridization, and immunohistochemistry demonstrated production of mature SOP in the cerebral ganglion. To elucidate the physiological action of SOP, we kept the tunicate for 2 d under the three different concentrations of seawater, 60, 100, and 130%, and measured the expression levels of SOP mRNA in the cerebral ganglion. The greatest expression of SOP mRNA was observed in the 60% seawater. In 60% seawater, but not in 100 or 130%, the tunicate mostly closed the atrial and branchial siphons. Therefore, we investigated the contractile effects of SOP on the siphons in vitro. SOP caused contractions in both siphons in a dose-dependent manner. Taken together, these results suggest that SOP acts to prevent the influx of a low concentration of seawater into the body and thus play an important role in osmoregulation.

Pituitary function after endonasal surgery for nonadenomatous parasellar tumors: Rathke's cleft cysts, craniopharyngiomas, and meningiomas.

BACKGROUND: Transsphenoidal surgery for parasellar nonadenomatous lesions has the possibility to either improve or worsen pituitary hormonal function. Herein we present the rates and risk factors of new hormonal failure and recovery in patients undergoing surgery for either an RCC, craniopharyngioma, or tuberculum sella meningioma. METHODS: All consecutive patients treated over an 8-year period by endonasal surgery for an RCC, craniopharyngioma, or tuberculum sella meningioma were analyzed. Patients treated with prior sellar radiotherapy were excluded. Preoperative and postoperative pituitary hormonal status was determined. Patient characteristics, tumor size, intraoperative and postoperative events, and extent of tumor resection were correlated with new or resolved hypopituitarism. RESULTS: In total, 50 patients with an RCC, 18 with a craniopharyngioma and 13 with tuberculum sellae meningioma, were analyzed. New anterior pituitary failure and permanent DI occurred as follows: in RCCs, 6% and 2%; in craniopharyngiomas, 31% and 39%; and in meningiomas, 9% and 0%. Overall, improved hormonal function occurred in 57% of patients with an RCC including recovery of one or more anterior axes in 9 (41%) of 22 patients and resolution of hyperprolactinemia in 12 (67%) of 18 patients; no patients with a craniopharyngioma or meningioma had resolution of hypopituitarism. Younger age was predictive of hormonal recovery in patients with an RCC (P = .026). CONCLUSIONS: New hypopituitarism after transsphenoidal surgery occurs in approximately one third of patients with a craniopharyngioma and in less than 10% of patients with an RCC or suprasellar meningioma. Hormonal function improves in the majority of patients undergoing drainage of an RCC but is unlikely to occur after removal of a craniopharyngioma or suprasellar meningioma.

Chronic osmotic stimuli increase salusin-beta-like immunoreactivity in the rat hypothalamo-neurohypophyseal system: possible involvement of salusin-beta on [Ca2+]i increase and neurohypophyseal hormone release from the axon terminals.

Salusin-alpha and -beta were recently discovered as bioactive endogenous peptides. In the present study, we investigated the effects of chronic osmotic stimuli on salusin-beta-like immunoreactivity (LI) in the rat hypothalamo-neurohypophyseal system. We examined the effects of salusin-beta on synaptic inputs to the rat magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and neurohypophyseal hormone release from both freshly dissociated SONs and neurohypophyses in rats. Immunohistochemical studies revealed that salusin-beta-LI neurones and fibres were markedly increased in the SON and the magnocellular division of the paraventricular nucleus after chronic osmotic stimuli resulting from salt loading for 5 days and dehydration for 3 days. Salusin-beta-LI fibres and varicosities in the internal zone of the median eminence and the neurohypophysis were also increased after osmotic stimuli. Whole-cell patch-clamp recordings from rat SON slice preparations showed that salusin-beta did not cause significant changes in the excitatory and inhibitory postsynaptic currents of the MNCs. In vitro hormone release studies showed that salusin-beta evoked both arginine vasopressin (AVP) and oxytocin release from the neurohypophysis, but not the SON. In our hands, in the neurohypophysis, a significant release of AVP and oxytocin was observed only at concentrations from 100 nm and above of salusin-beta. Low concentrations below 100 nm were ineffective both on AVP and oxytocin release. We also measured intracellular calcium ([Ca(2+)](i)) increase induced by salusin-beta on freshly-isolated single nerve terminals from the neurohypophysis devoid of pars intermedia. Furthermore, this salusin-beta-induced [Ca(2+)](i) increase was blocked in the presence of high voltage activated Ca(2+)channel blockers. Our results suggest that salusin-beta may be involved in the regulation of body fluid balance by stimulating neurohypophyseal hormone release from nerve endings by an autocrine/paracrine mechanism.

Transient reduction in the posterior pituitary bright signal preceding water intoxication in a malnourished child.

We describe a 4 year-old boy with hypothalamic dysfunction and weight loss, attributed to psychosocial deprivation. Reduced intensity of the posterior pituitary bright signal (PPBS) on MRI, associated with a normal urinary concentrating ability, was documented in the 24 hours prior to the development of the syndrome of inappropriate secretion of antidiuretic hormone (ADH) and severe hyponatraemia. The PPBS was normal on MRI 2 months later, following weight gain and resolution of the other hypothalamic abnormalities. This report shows that the abnormalities of ADH associated with decreased intensity of the PPBS include increased secretion and abnormal regulation as well as ADH deficiency. The association of osmotically unregulated ADH secretion with undernutrition and stress suggests that particuar caution should be used when fluid intake in such children is not driven by thirst.

Vasopressin-induced taurine efflux from rat pituicytes: a potential negative feedback for hormone secretion.

Previous work on the whole neurohypophysis has shown that hypotonic conditions increase release of taurine from neurohypophysial astrocytes (pituicytes). The present work confirms that taurine is present in cultured pituicytes, and that its specific release increases in response to a hypotonic shock. We next show that vasopressin (VP) and oxytocin (OT) also specifically release taurine from pituicytes. With an EC(50) of approximately 2 nm, VP is much more potent than OT, and the effects of both hormones are blocked by SR 49059, a V(1a) receptor antagonist. This pharmacological profile matches the one for VP- and OT-evoked calcium signals in pituicytes, consistent with the fact that VP-induced taurine efflux is blocked by BAPTA-AM. However, BAPTA-AM also blocks the taurine efflux induced by a 270 mosmol l(-1) challenge, which per se does not evoke any calcium signal, suggesting a permissive role for calcium in this case. Nevertheless, the fact that structurally unrelated calcium-mobilizing agents and ionomycin are able to induce taurine efflux suggests that calcium may also play a signalling role in this event. It is widely accepted that in hypotonic conditions taurine exits cells through anionic channels. Antagonism by the chloride channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) suggests the same pathway for VP-induced taurine efflux, which is also blocked in hypertonic conditions (330 mosmol l(-1)). Moreover, it is likely that the osmosensitivity of the taurine channel is up-regulated by calcium. These results, together with our in situ experiments showing stimulation of taurine release by endogenous VP, strengthen the concept of a glial control of neurohormone output.

Effects of glucagon-like peptide-1 (7-36) amide on neurohypophysial hormone secretion induced by acute hyperosmotic challenge.

This study was designed to investigate possible effects of glucagon-like peptide-1 (7-36) amide on the vasopressin and oxytocin release induced by acute peripheral or central osmotic stimulation. In the first series of experiments, rats were injected intraperitoneally with the isotonic (0.15 M) or hypertonic (1.5 M) NaCl solution and then, intracerebroventricularly, with either 1 microg glucagon-like peptide-1 (7-36) amide dissolved in 5 microl of isotonic saline or with the vehicle only. In the second study, 1 microg glucagon-like peptide-1 (7-36) amide, dissolved in isotonic or hypertonic (0.6 M) saline, was injected into the cerebroventricular system. Control rats were treated with isotonic or hypertonic saline only. All the animals were decapitated 10 min after the intracerebroventricular injection. Glucagon-like peptide-1 (7-36) amide enhanced significantly the basal secretion of vasopressin and oxytocin. Moreover, this peptide increased additionally the release of both neurohypophysial hormones stimulated previously by peripheral osmotic challenge. On the other hand, the peptide increased the oxytocin but not vasopressin secretion brought about by an intracerebroventricular injection of hypertonic saline thus suggesting that the central osmotic stimulation decreases the sensitivity of vasopressin neurons to glucagon-like peptide-1 (7-36) amide. It is concluded that glucagon-like peptide-1 (7-36) amide may affect the secretory activity of the hypothalamo-neurohypophysial system under acute osmotic challenge.

Early osmoregulatory signals in the control of water intake and neurohypophyseal hormone secretion.

Dehydrated dogs inhibit secretion of vasopressin (VP) within minutes after drinking water, before plasma osmolality (pOsm) diminishes. In recent studies, we found that water ingestion by rats similarly inhibits VP and oxytocin (OT) secretion rapidly, before pOsm is diluted. Adult male rats were infused with 1 M NaCl (2 ml/h iv) for 240 min to stimulate VP and OT secretion. After 220 min of infusion, rats were given water or isotonic saline (IS) to drink for 5 min, and blood samples were taken 5 and 15 min later. Plasma levels of VP (pVP) and OT (pOT) were much lower when rats ingested water instead of IS, even though rats drank comparable amounts of both fluids ( approximately 5.5 ml) and pOsm was not significantly affected in either case. In another study, rats were infused with 1 M NaCl (2 ml/h iv) for 120 min before receiving 4-ml gastric loads of either 0.5 M NaCl (HS) or IS; blood samples taken 25 min later showed that pVP and pOT were much higher when rats were given gastric loads of HS instead of IS, even though pOsm was not significantly altered. Comparable results were obtained when gastric loads of HS or IS were given to rats that had been deprived of drinking water overnight. Other dehydrated rats treated similarly but given access to drinking water consumed much more when they had been given gastric loads of HS instead of IS. Collectively, these and other findings suggest the importance of early signals, perhaps from hepatoportal osmoreceptors or Na(+) receptors, in the control of VP and OT secretion and water intake in rats.

Early osmoregulatory stimulation of neurohypophyseal hormone secretion and thirst after gastric NaCl loads.

Cerebral osmoreceptors mediate thirst and neurohypophyseal secretion stimulated by increases in the effective osmolality of plasma (P(osmol)). The present experiments determined whether an intragastric load of hypertonic saline (ig HS; 0.5 M NaCl, 4 ml) would potentiate these responses before induced increases in P(osmol) in the general circulation could be detected by cerebral osmoreceptors. Adult rats deprived of water overnight and then given intragastric HS consumed much more water in 15-30 min than rats given either pretreatment alone, even though systemic P(osmol) had not yet increased significantly because of the gastric load. In other rats pretreated with an intravenous infusion of 1 M NaCl (2 ml/h for 2 h), plasma levels of vasopressin and oxytocin were considerably elevated 15 and 25 min after intragastric HS treatment, whereas systemic P(osmol) was not increased further. These and other findings are consistent with previous reports that hepatic portal osmoreceptors (or Na(+) receptors) stimulate thirst and neurohypophyseal hormone secretion in euhydrated rats given gastric NaCl loads and indicate that these effects are potentiated when animals are dehydrated.

The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus.

Methylenedioxymethamphetamine (MDMA, 'ecstasy'), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by MDMA or one of its metabolites has been investigated in vitro. Release of both oxytocin and vasopressin from isolated hypothalami obtained from male Wistar rats was determined under basal conditions and following potassium (40 mM) stimulation. The results were compared with those obtained for basal and stimulated release in the presence of MDMA or metabolites in the dose range 1 microM to 100 pM (n=5 - 8) using Student's t-test with Dunnett's correction for multiple comparisons. All compounds tested affected neurohypophysial hormone release, HMMA (4-hydroxy-3-methoxymethamphetamine) and DHA (3,4-dihydroxyamphetamine) being more active than MDMA, and DHMA (3,4-dihydroxymethamphetamine) being the least active. The effect on vasopressin release was greater than that on oxytocin. In the presence of HMMA the ratio test:control for basal release increased for vasopressin from 1.1+/-0.16 to 2.7+/-0.44 (s.e.m., P<0.05) at 10 nM and for oxytocin from 1.0+/-0.05 to 1.6+/-0.12 in the same hypothalami. For MDMA the ratio increased to 1.5+/-0.27 for vasopressin and to 1.28+/-0.04 for oxytocin for 10 nM. MDMA and its metabolites can stimulate both oxytocin and vasopressin release in vitro, the response being dose dependent for each drug with HMMA being the most potent.

Neurohypophysial hormone secretion in hyperprolactinaemic women.

Prolactin (PRL) has been reported to promote antidiuresis and increase intestinal water-electrolyte absorption, whereas osmolar changes have been shown to influence PRL secretion. However, the mechanisms of action of PRL on the salt-water balance remain unclarified. The present clinical study targeted the effects of hyperprolactinaemia on the secretion of arginine-8-vasopressin (AVP), oxytocin (OXT) and cortisol. Plasma AVP and OXT were measured by radioimmunoassay, and cortisol by fluorimetry. In healthy women (21-39 y, n=6), an oral water load (OWL, 20 ml/bw) significantly suppressed the plasma levels of AVP, OXT and cortisol, and the PRL level too tended to decrease. In hyperprolactinaemic females (22-41 y, n=6, three with pituitary adenomas), water retention was registered following an OWL, together with paradoxical AVP and OXT level increases, whereas the cortisol response remained normal, and the PRL level did not change at all. Histamine (0.5 mg sc) stimulated the release of AVP, OXT and cortisol in the control and hyperprolactinaemic groups alike. These data suggest that alterations in AVP and OXT hypersecretion may contribute to the water retention in hyperprolactinaemia.