The influence od melatonin receptors antagonists, luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT), on melatonin-dependent vasopressin and adrenocorticotropic hormone (ACTH) release from the rat hypothalamo-hypophysial system. In vitro and in vivo studies.

Melatonin exerts its biological role acting via G protein-coupled membrane receptors - MT1 and MT2, as well as through cytoplasmic and/or nuclear receptors. Melatonin has previously been shown to change vasopressin (AVP) and adrenocorticotropic hormone (ACTH) secretion dependently on its concentration. To determine whether the response of vasopressinergic neurones to different concentrations of melatonin is mediated through the membrane MT1 and/or MT2 receptors, the influence of luzindole - an antagonist of both MT1 and MT2 receptors, and 4-phenyl-2-propionamidotetralin (4-P-PDOT) - a selective MT2 receptor antagonist, on melatonin-dependent AVP release from the rat hypothalamo-neurohypophysial (H-NH) system was studied in vitro (melatonin at the concentrations of 10(-9), 10(-7) and 10(-3) M) and in vivo (melatonin at the concentrations of 10(-9) and 10(-7) M). Moreover, the second goal of this study was to find out whether melatonin receptors MT1 and/or MT2 are involved in the regulation of ACTH and corticosterone secretion into the blood. We have demonstrated that melatonin, at the concentrations of 10(-9) and 10(-7) M, significantly inhibited AVP secretion from isolated rat H-NH explants when antagonists solvent (i.e. 0.1% DMSO) was present in the medium. Neither luzindole, nor 4-P-PDOT, applied without melatonin, did influence AVP release in vitro. Luzindole applied together with melatonin (10(-7) M and 10(-9) M) significantly suppressed melatonin-dependent effect, while 4-PPDOT did not eliminate the inhibitory influence of 10(-7) M and 10(-9) M melatonin on AVP secretion from isolated rat H-NH explants. Melatonin at a concentration of 10(-3) M significantly increased AVP release when the H-NH explants were incubated in the medium containing luzindole or 4-P-PDOT. Under present experimental in vivo conditions, infused intracerebroventricularly (i.c.v.) melatonin, at a concentration close to its physiological level in the blood, significantly diminished AVP secretion into the blood, however, at higher concentration (10(-7) M) it remained inactive in this process. Moreover, melatonin at both concentrations of 10(-9) M and 10(-7) M, was able to inhibit AVP secretion into the blood (and increase its neurohypophysial content) when animals were previously i.c.v. injected with 4-P-PDOT, but not with luzindole. Blood plasma concentration of ACTH was diminished significantly by 10(-7) M melatonin in DMSO-infused, but not in luzindole- or 4-P-PDOT-injected rats, however, it remained inactive in modifying the corticosterone blood plasma concentrations in any of the studied subgroups. The present study demonstrates that subtype MT1 membrane receptor may contribute to the inhibitory effect of physiological concentration of melatonin on functional regulation of vasopressinergic neurones in the rat. However, for the stimulatory effect of pharmacological dose of the hormone on AVP secretion in vitro, mechanisms different from membrane MT1/MT2 receptors are involved. The present experiment do not determines whether MT1 and/or MT2 receptors affect the function of the rat pituitary-adrenal cortex axis.

Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of gonadotrophin-releasing hormone (GnRH), its analogues and melatonin.

The influence of gonadotrophin-releasing hormone (GnRH) and its analogues (i.e., agonist and antagonist) on vasopressin (VP) release from the rat hypothalamo-neurohypophysial (H-N) system was studied both in vitro and in vivo. Additionally, it was determined whether the possible response of vasopressinergic neurones to these peptides could be modified by melatonin through a cAMP-dependent mechanism. In this study we demonstrate, for the first time, that the highly selective GnRH agonist (i.e., [Des-Gly(10),D-His(Bzl)(6),Pro-NHEt(9)]-LHRH; histrelin) stimulates the release of VP from the rat H-N system, while native GnRH and its antagonist remain inactive in modifying this process in vitro. Melatonin significantly inhibited basal and histrelin-induced release of VP in vitro, but displayed no significant influence on VP secretion when GnRH or its antagonist were present in a medium. Melatonin fully suppressed forskolin-stimulated VP release from the rat H-N system. On the other hand, addition of forskolin to a medium containing both histrelin and melatonin did not further alter the inhibitory influence of melatonin on the histrelin-dependent release of VP in vitro. After intracerebroventricular (i.c.v.) infusion of native GnRH or its agonist, blood plasma VP concentration was significantly higher than in control animals, which was accompanied by decreased content of the hormone in the neurohypophysis. Intravenous (i.v.) injection of melatonin did not change, in any subgroup, blood plasma VP concentration, when compared to the vehicle-injected rats. However, the neurohypophysial levels of the hormone were significantly higher after melatonin injection in control, GnRH- and histrelin-infused animals. Our present results suggest that activation of the GnRH receptor in the hypothalamus is involved in stimulation of VP secretion from the rat H-N system. We have also shown that melatonin, at a concentration close to its physiological level in the blood, significantly reduces the in vitro response of vasopressinergic neurones to a GnRH agonist - histrelin; this effect of melatonin could be mediated through intracellular processes that involve, among others, the cAMP-dependent mechanism.

Experimental hypothyroidism increases content of collagen and glycosaminoglycans in the heart.

The connective tissue matrix of the heart remains under regulatory influence of the thyroid hormones. Some conflicting data describe the connective tissue changes in subjects with thyroid gland disorders. The aim of the study was to assess the changes of the connective tissue accumulation in the heart of rats in the state of hypothyroidism and to answer the question whether TSH is involved in mechanism of the observed phenomena. Hypothyroidism in rats was induced by methylotiouracil treatment or by thyreoidectomy. The thyroid hormones [freeT3 (fT3), freeT4 (fT4)] and pituitary TSH were measured in plasma with radioimmunological method. The glycosaminoglycans (GAG) and total collagen were measured in heart muscle of both left and right ventricles. Cells from the rat's heart were isolated and cultured. The cells were identified as myofibroblasts by electron microscopy method. The effects of TSH in concentrations ranging from 0.002 to 20 mIU/ml, on connective tissue accumulation in heart myofibroblasts cultures were tested. The primary hypothyroidism was developed both in groups with thyroidectomy and with methylthiouracil. The levels of fT3 and fT4 both in rats with thyreoidectomy and animals treated with methylthiouracil were decreased and TSH level in these two experimental groups was elevated. In the heart of the rats with experimental hypothyroidism increased content of both GAG and collagen was found. Myofibroblast number in culture was increased by TSH. Regardless of the method of its induction, hypothyroidism increased collagen and GAG contents in the heart. TSH is not involved in regulation of collagen and glycosaminoglycans accumulation in the heart of rats affected with primary hypothyroidism.

Effect of melatonin on the vasopressin secretion as influenced by tachykinin NK-1 receptor agonist and antagonist: in vivo and in vitro studies.

The aim of the present study was to investigate the influence of melatonin on vasopressin (AVP) release from the rat hypothalamo-neurohypophysial (H-NH) system, both in vivo and in vitro, possibly modified by the peptide NK-1 and/or NK-2 receptor agonists and antagonists. Highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, has been shown to enhance the AVP release from isolated rat H-NH system in vitro, while the NK-1 receptor antagonist--(Tyr(6),DPhe(7),D-His(9))-Substance P (6-11) as well as the NK-2 receptor selective agonist--(beta-Ala(8))-Neurokinin A (4-10) and antagonist--(Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying AVP secretion. Melatonin inhibited basal release of AVP but was not able to reduce significantly the in vitro response of vasopressinergic neurones to NK-1 receptor agonist. After intracerebroventricular (icv) administration, substance P (SP), neurokinin A (NKA) and the NK-1 receptor agonist (all at the concentration of 10(-7) M/L) significantly enhanced plasma AVP concentration. Such stimulatory effect of the latter peptide on AVP output from the eurohypophysis was reduced by an intravenous (iv) injection of melatonin, which itself (at a concentration of 5 ng/ml) caused a significant decrease in AVP release 10 min after injection. The inhibitory influence of melatonin on the AVP secretion was absent in rats injected icv with both tachykinin receptors antagonists, the NK-2 receptor agonist or NKA. The present data indicate a distinct role for NK-1 receptor in NKA/SP-mediated regulation of AVP release from the rat H-NH system. They have also shown that, under present experimental conditions, the stimulatory effect of NK-1 receptor activation on AVP secretion into the blood is sensitive to inhibitory influence of melatonin.

Role of tachykinin receptors and melatonin in oxitocin secretion from isolated rat hypothalmo-neurohypophysial system.

Present investigations were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on oxytocin (OT) release from isolated rat hypothalamo-neurohypophysial (H-N) system as well as to determine whether the tachykinin NK-1 and/or NK-2 receptors contribute to the response of oxytocinergic neurons to melatonin. The results show, for the first time, that highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, enhances while the NK-1 receptor antagonist (Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11) - sendide - diminishes significantly OT secretion; the latter peptide was also found to antagonize the substance P-induced hormone release from isolated rat H-N system, when used at the concentration of 10(-7) M/L. Melatonin significantly inhibited basal and substance P-stimulated OT secretion. Neurokinin A and the NK-2 receptor selective agonist (beta-Ala(8))-Neurokinin A (4-10) as well as the NK-2 receptor antagonist (Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying OT release from the rat H-N system in vitro. The present data indicate a distinct role for tachykinin NK-1 (rather than NK-2) receptor in tachykinin-mediated regulation of OT secretion from the rat H-N system. Under present experimental conditions, however, a role of respective tachykinin receptors in the response of oxytocinergic neurons to melatonin has not been found.

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.

Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and cardiovascular functions under hypo- or normotensive hypovolaemia in the rat.

To date, glucagon-like peptide 1(7-36) amide (tGLP-1) has been found to affect the neurohypophysial and cardiovascular functions in normotensive and normovolaemic rats. The aim of the present study was to investigate possible effects of tGLP-1 on the mean arterial blood pressure and the release of vasopressin and oxytocin under conditions of blood volume depletion in the rat. In the first series of experiments, the animals were injected i.p. with either 0.15 M saline or 30% polyethylene glycol (PEG). PEG caused an 18% reduction of blood volume 1 h after injection. No significant changes in the mean arterial blood pressure were found in either normo- or hypovolaemic rats during the experiment. tGLP-1 injected i.c.v. at a dose of 1 microg/5 microl 1 h after the i.p. injection increased similarly the arterial blood pressure in normo- and hypovolaemic rats. The plasma vasopressin/oxytocin concentrations were markedly elevated in hypovolaemic animals and tGLP-1 further augmented the release of both hormones. In the second study, hypovolaemia was induced by double blood withdrawal. The haemorrhage resulted in a marked decrease of the mean arterial blood pressure and in the elevated plasma vasopressin/oxytocin concentrations. tGLP-1 injected immediately after the second blood withdrawal increased the arterial blood pressure. In parallel, tGLP-1 enhanced significantly vasopressin and oxytocin secretion when compared with haemorrhaged, saline-injected rats. The results of this study indicate that tGLP-1 may affect the arterial blood pressure and the secretion of neurohypophysial hormones under pathological conditions brought about by blood volume depletion.

tGLP-1 and release of vasopressin and oxytocin from the isolated rat hypothalamo-neurohypophysial system: effects of a tGLP-1 receptor agonist and antagonist.

To date, glucagon-like peptide-1 (7-36) amide (tGLP-1) has been found to enhance the vasopressin and oxytocin secretion in vivo but not in vitro (i.e., when the isolated neurointermediate lobe of the pituitary was used for experiments). The goal of this study was to investigate whether tGLP-1 can influence the function of the hypothalamo-neurohypophysial complex in vitro. Also, the effect of a tGLP-1 agonist, exendin-4, and antagonist, exendin-(9-39), on the release of vasopressin/oxytocin from the isolated rat hypothalamo-neurohypophysial complex was tested. tGLP-1 enhanced the basal but not the potassium-stimulated release of vasopressin and oxytocin from the hypothalamo-neurohypophysial complex. On the other hand, tGLP-1 failed to affect the release of both hormones from the isolated neurointermediate lobe. The tGLP-1 agonist increased the secretion of oxytocin and vasopressin from the hypothalamo-neurohypophysial system whilst the tGLP-1 antagonist completely abolished the stimulatory effect of tGLP-1 on the secretion of both hormones. It is concluded that tGLP-1 affects the function of vasopressin- and oxytocinergic neurones through specific hypothalamic receptors.

Effects of centrally or systemically injected glucagon-like peptide-1 (7-36) amide on release of neurohypophysial hormones and blood pressure in the rat.

The present study was designed to compare the effects of glucagon-like peptide-1 (7-36) amide (GLP-1) injected centrally or systemically in a dose range of 10-10000 ng on the vasopressin and oxytocin release as well as the blood pressure in the rat. The urethane-anaesthetised Wistar male and female rats were fitted with venous as well as arterial catheters and, in the second study, additionally with the intracerebroventricular cannula. The arterial blood pressure was monitored throughout the experiment. The plasma vasopressin/oxytocin concentrations were measured in blood samples taken 15 min before and 5, 15 and 30 min after the intravenous or intracerebroventricular GLP-1 injection. No gender-dependent differences were seen as to the GLP-1 effect on the blood pressure or the hormone release. GLP-1 administered centrally or systemically at low doses (10 or 100 ng) either showed a hypertensive or biphasic (an increase followed by a decrease in the blood pressure) effect. On the other hand, 1000 or 10000 ng GLP-1 caused a clear increase of the blood pressure regarding the way of injection. When injected systemically, GLP-1 increased the release of both neurohypophysial hormones. When injected centrally, however, GLP-1 either enhanced or, at low doses, significantly reduced the plasma vasopressin/oxytocin levels. The effect on the blood pressure seems to be independent of the possible pressor effect of endogenous vasopressin. It is concluded that GLP-1 may modulate the function of the hypothalamo-neurohypophysial system as well as the cardiovascular system through both the central and systemic mechanisms.

The effect of melatonin on vasopressin release under stress conditions in pinealectomized male rats.

The findings here reported showed that the response of vasopressinergic neurons to immobilization stress is augmented by melatonin. The effectiveness of melatonin in functional modification of these neurons' activity under conditions of stress changes after pineal removal.

Effects of methylphenidate on oxytocin and vasopressin levels in pinealectomized rats during light-dark cycle.

Although previous reports have shown that methylphenidate (MPH), in addition to its known behavioral effect, can influence the hypothalamo-pituitary-adrenal axis by increasing the plasma ACTH, the pineal gland seems to be involved in neuroendocrinological processes too, e.g., in hypothalamic synthesis and release of oxytocin (OXY) and vasopressin (AVP). Therefore, a study was performed to measure the OXY and AVP content of the hypothalamus, neurohypophysis, and plasma after application of MPH in the morning and evening in pinealectomized (PE) as well as sham-operated control (SO) rats. Pinealectomy influenced both the daily pattern (reversed in the neurohypophysis) and the levels of OXY and AVP. Starting from this different situation, application of MPH produced diverse effects. Hypothalamus: PE, increase in both hormones in the morning and evening; SO, decrease in morning OXY level. Neurohypophysis: PE, increase in morning OXY level; SO, decrease in both hormones even though in the morning only. Plasma: PE, decrease in morning OXY concentration; SO, increase in both hormones in the morning and decrease in the evening. The present results indicate that MPH application influences the hypothalamo-neurohypophysial system. Furthermore, the hypothesis has been supported that this influence may be dependent on the circadian activity of the pineal gland as well.

Neurohypophyseal vasopressin in the Syrian hamster: response to short photoperiod, pinealectomy, melatonin treatment, or osmotic stimulation.

In the present study, the effect of photoperiod on vasopressin content in the pituitary neurointermediate lobe (NIL), as well as the ability of pinealectomy to prevent and melatonin to mimic the short photoperiod-induced changes in NIL vasopressin were studied in male Syrian hamsters. The ability of melatonin to modify the hyperosmotically stimulated vasopressin release was also determined. Exposure to short photoperiod (SD) for 4 or 10 weeks increased vasopressin content in the hamster NIL. In long photoperiod (LD)-exposed hamsters, pinealectomy induced a decrease in NIL vasopressin content, whereas no effect of melatonin injections on vasopressin storage in the NIL was detected. In SD-exposed animals, pineal removal failed to alter vasopressin content in the NIL. Hypertonic saline administration led to the expected decrease in vasopressin content in the NIL both in vehicle- and melatonin-treated animals. The hyperosmotically stimulated release of vasopressin was not modified by previous treatment with melatonin. The data from the present study show that, in male Syrian hamsters, exposure of animals to SD increases the vasopressin content in the posterior pituitary, but these changes appear not to be mediated by SD-induced changes in melatonin secretion. Furthermore, the exposure of animals to SD prevents the pinealectomy-induced changes in NIL vasopressin content. Melatonin does not modify the hyperosmotically stimulated vasopressin release in the male Syrian hamster.

The effect of melatonin on suckling-induced oxytocin and prolactin release in the rat.

There is growing evidence that melatonin (MEL) inhibits oxytocin (OT) release when used in a low dose, while higher doses stimulate the release of the hormone in the rat. In the present study we investigated the effect of exogenous MEL, administered intracerebroventricularly (ICV), on suckling-induced OT and prolactin (PRL) release in the urethane-anesthetized rat. Lactating rats suckled by 8-12 pups were studied on days 8-12 of postpartum, and lactating pups-deprived rats on the same days of postpartum served as a control. Plasma OT and PRL levels as well as hypothalamic and neurohypophyseal OT contents were measured by RIA. Suckling stimulated the secretion of both OT and PRL. The ICV injection of 1 ng/ml MEL produced a significant inhibition of suckling-induced OT as well as PRL secretion. Melatonin in doses of 100 ng/ml or 10 micrograms/ml did not modify the OT release but significantly inhibited PRL release brought about by suckling; 10 pg/ml of MEL was not effective in this regard. Thus, exogenous MEL seems to inhibit suckling-induced OT as well as PRL secretion when applied at doses regarded to be in the range of the physiological level; when applied in higher doses, it was shown not to influence the release of OT following physiological stimulation such as suckling.

The influence of vasopressin or oxytocin on thyroid-stimulating hormone and thyroid hormones' concentrations in blood plasma of euthyroid rats.

The effects of arginine vasopressin (AVP) and oxytocin (OT) upon thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) release were studied in euthyroid rats. Intracerebroventricular (i.c.v.) infusion of AVP in doses of 0.5 ng or 5 ng led to significant increases in plasma levels of TSH as well as FT4 and FT3. The effects of OT injected i.c.v. in similar doses were not consistent (there was no parallel between the changes of respective hormones plasma levels). It may be concluded that vasopressin modulate the pituitary-thyroid system function; AVP is probably a physiological stimulator of TSH and thyroid hormones secretion.

Thyrotropin-releasing hormone (TRH) inhibits vasopressin and oxytocin release from rat hypothalamo-neurohypophysial explants in vitro.

Incubation of hypothalamo-neurohypophysial explants in Locke's solution containing 28 nM/L thyrotropin-releasing hormone (TRH) resulted in an inhibition of vasopressin and oxytocin secretion during depolarization due to excess potassium. These data suggest the involvement of TRH in the regulatory mechanisms of vasopressin and oxytocin release; the inhibitory effect of TRH cannot be excluded.

Luliberin inhibits the release of Oxytocin from hypothalamo-neurohypophysial system in dehydrated but not in euhydrated or haemorrhaged rats.

Rats euhydrated, dehydrated for two days or haemorrhaged were given intracerebroventricularly (i.c.v.) luteinizing hormone releasing hormone (LH-RH) in a daily dose of 100 ng dissolved in 10 microl of 0.9 % sodium chloride. In euhydrated rats, a single i.c.v. dose of LH-RH as well as the daily i.c.v. treatment with LH-RH for two days did not affect significantly either the plasma oxytocin concentrations or the hypothalamo-neurohypophysial oxytocin content. In animals dehydrated for two days and treated with LH-RH the increase in plasma oxytocin was almost suppressed and the depletion of neurohypophysial hormone content was significantly less marked. Luliberin treatment had no effect on the hypothalamo-neurohypophysial content of oxytocin as well as on plasma oxytocin concentration in haemorrhaged rats. We suggest that LH-RH may have a regulatory role in the hypothalamo-neurohypophysial oxytocinergic system, especially under hyperosmotic dehydration.

Melatonin inhibits oxytocin and vasopressin release from the neurointermediate lobe of the hamster pituitary.

The aim of this investigation was to study whether melatonin affects the release of oxytocin and vasopressin by the pituitary neurointermediate lobe of the Syrian hamster in vitro. The effect of melatonin was studied on the unstimulated (pre- and post-K+ -stimulated) release of oxytocin and vasopressin and on the response to K+ stimulation. Melatonin significantly inhibited unstimulated release of these hormones in all concentrations (10(-11) M, 10(-9) M and 10(-7) M) studied. K+ -stimulated release of oxytocin and vasopressin was significantly decreased by the 10(-9) M dose of melatonin. It is concluded that melatonin is active in modifying the release of these peptides in the Syrian hamster neurointermediate lobe, as it has been previously demonstrated in the rat hypothalamus.

Thyrotropin-releasing hormone (TRH) modifies oxytocin release from the hypothalamo-neurohypophysial system in salt-loaded rats.

Rats drinking ad libitum tap water or hypertonic (i.e. 2%) sodium chloride solution were given intracerebroventricularly (i.c.v.), for three days, thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10 microliters of 0.9% sodium chloride. Treatment with TRH resulted in significantly decreased hypothalamic oxytocin content in both euhydrated (i.e. given tap water ad libitum) and salt-loaded rats. In rats drinking tap water, neurohypophysial oxytocin content decreased. Plasma oxytocin concentration was distinctly elevated under TRH treatment in rats euhydrated but, on the contrary, decreased in salt-loaded rats as compared with animals similarly drinking hypertonic saline but not TRH-treated. The present data suggest that TRH may be involved in some regulatory processes related to oxytocin biosynthesis and release from the rat hypothalamo-neurohypophysial system.

Insulin-like immunoreactivity (IRI) in the rat hypothalamo-neurohypophysial system: effect of dehydration and haemorrhage.

Hypothalamic IRI was not affected in haemorrhaged rats, but diminished considerably in the dehydrated ones. In the neurohypohysis, IRI was distinctly higher both in dehydrated and haemorrhaged rats, i.e., under disorders which stimulated vasopressin and/or oxytocin release. It is suggested that insulin-like substance(s) may be someway involved in regulation of vasopressin or oxytocin secretion.

Thyrotropin-releasing hormone (TRH) inhibits vasopressin release from hypothalamo-neurohypophysial system of rats drinking hypertonic saline.

Rats drinking ad libitum tap water or hypertonic (i.e. 2%) sodium chloride solution were given intracerebroventricularly (i.c.v.) for three days, thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10 microliters of 0.9% sodium chloride. Treatment with TRH resulted in significantly increased hypothalamic vasopressin content in both euhydrated (i.e. given tap water ad libitum) and salt-loaded rats. In rats given hypertonic saline, neurohypophysial vasopressin content increased. Plasma vasopressin concentration was distinctly diminished under TRH treatment, the respective difference being significant, however, barely in salt-loaded rats. The present data suggest that TRH may be involved in some regulatory processes related to vasopressin biosynthesis and release from the rat hypothalamo-neurohypophysial system.