Search Results

You are looking at 1 - 9 of 9 items for

  • Author: Ulrich Knigge x
Clear All Modify Search
Restricted access

Ulrich Knigge and Jørgen Warberg

Abstract.

The neurotransmitter histamine participates in the neuroendocrine regulation of pituitary hormone secretion by an indirect action at a hypothalamic level where histaminergic neurons are abundant. The effect of histamine is caused by activation of postsynaptic H1- or H2-receptors. Histamine stimulates the secretion of ACTH, β-endorphin (mediated by CRH and AVP), α-MSH (mediated by dopamine and peripheral catecholamines), and PRL (mediated by dopamine, serotonin and AVP), and participates in the stress-induced release of these hormones and possibly in the suckling- and estrogen-induced PRL release. The release of GH and TSH is predominantly inhibited by histamine; however, uncertainty exists regarding its role and the hypothalamic factors involved. Histamine increases the secretion of LH in females (mediated by GnRH), and may be involved in the mediation of the estrogen-induced LH surge. AVP and oxytocin are stimulated by histamine, probably by an effect in the supraoptic and paraventricular nuclei of the hypothalamus.

Restricted access

Andreas Kjær, Ulrich Knigge and Jørgen Warberg

Kjær A, Knigge U, Warberg J. Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors. Eur J Endocrinol 1994;131:391–7. ISSN 0804–4643

We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10–14-fold. Pretreatment with the selective V1- receptor antagonists [1-(p-t-butyl-β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-d-arginine] vasopressin or [1-(β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vasopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(β-mercapto-β, β-cyclopentamethylene propionic acid)-2-d-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-d-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stressinduced secretion of PRL, and that the AVP receptor involved is primarily of the V1 -type or similar to this.

Andreas Kjær, Department of Medical Physiology, Division of Endocrinology and Metabolism, The Panum Institute (Building 12.3), University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

Restricted access

Ulrich Knigge, Steen Matzen and Jørgen Warberg

Abstract. The effects on prolactin secretion of histamine H2-receptor antagonists infused intracerebroventricularly were studied in urethane anaesthetized male rats. A dose of 1.6 μmol cimetidine stimulated basal prolactin secretion and did not affect the histamine-induced release, whereas 0.4 μmol cimetidine inhibited basal and histamine-stimulated prolactin secretion. 0.1 μmol cimetidine had no effect. The more potent H2-receptor antagonist ranitidine at doses of 0.1, 0.4, 1.6 μmol had no effect on basal prolactin secretion, whereas 0.4 and 1.6 μmol inhibited the histamine-stimulated secretion completely. SKF-92408, a compound resembling cimetidine in chemical structure but devoid of H2-receptor antagonist activity, stimulated basal prolactin secretion at a dose of 1.6 μmol, but had no effect on the histamine-induced release or at a dose of 0.4 μmol. The H2-receptor antagonists metiamide and oxmetidine (1.6 μmol) stimulated basal prolactin secretion and did not prevent the response to histamine. A dose of 0.4 or 1.6 μmol imidazole (the ring structure contained in cimetidine, SKF-92408, metiamide, and oxmetidine) had no effect on basal or histamine-stimulated prolactin secretion. The findings indicate that cimetidine stimulates prolactin secretion by a non-specific action when infused centrally at high doses. In contrast, when infused at lower doses cimetidine inhibits the basal and histamine-stimulated secretion by blockade of H2-receptors. The prolactin-stimulatory action of cimetidine was not due to an H2-agonist effect, since ranitidine did not prevent the response. Cimetidine did not stimulate prolactin secretion via an effect on the dopaminergic system, since the drug had no effect on the dopamine concentration in hypophysial portal blood or in hypothalamic tissue and since inhibition of the dopamine synthesis by α-methyl-p-tyrosine did not prevent the cimetidine-induced prolactin release.

Restricted access

Andreas Kjær, Ulrich Knigge and Jørgen Warberg

Abstract.

We investigated in male rats whether the prolactin releasing effect of systemically infused histamine might be attributed to a vasodilatatory action of the compound. Intraarterial infusion of histamine (3.8 μmol) over 1 min increased the plasma PRL 10-fold. This effect was prevented by prior ia infusion of the H1 receptor antagonist mepyramine and slightly augmented by prior ia infusion of the H2 receptor antagonist cimetidine. At the same time histamine caused an immediate 38% decrease in mean arterial blood pressure, which remained 15% below the initial level during the rest of the 60-min observation period. The depressor effect of histamine was prevented by pretreatment with mepyramine and partly prevented for the first 5 min by pretreatment with cimetidine. Since the H1 receptor seemed to be the predominant mediator of the histamine-induced hypotension and PRL release, a causative interaction is possible. However, when the histamine-induced decrease in blood pressure was prevented by simultaneous iv loading with saline the PRL response to histamine was still evident. Furthermore, when the histamine-induced decrease in blood pressure was mimicked by ia infusion of the vasodilator nitroprusside no effect was observed on PRL secretion. We conclude that the histamine-induced stimulation of PRL secretion is independent of the profound depressor action of the amine.

Restricted access

Steen Matzen, Ulrich Knigge and Jørgen Warberg

Abstract. General anaesthesia has been reported to interact with neuroendocrine functions leading to large variations in basal and stimulated plasma levels of several hormones, but the findings are often contradictory. In the present investigation we have attempted to clarify the importance of the experimental procedure when evaluating the influence of anaesthetics on the secretion of PRL and LH in male rats. One group of rats (non-adapted) were anaesthetized (ip) with pentobarbital (P), urethane (U), ketamine (A), or althesin (A) without being accustomed to the laboratory environment prior to anaesthesia. Another group of rats (adapted) were kept for 90 min in their individual cages before induction of anaesthesia with P or U. In non-adapted rats the plasma concentration of PRL declined rapidly during the first 30 min following administration of all anaesthetics or saline (controls) and attained a steady level after 60 min. Except for a brief rise following U injection, the LH concentration was not affected by anaesthesia in the non-adapted rats. In adapted rats, the concentration of both PRL and LH declined markedly during the pre-anaesthetic adaptation period and had stabilized at the end of that period. Following administration of U, P or saline, no further changes in the hormone concentrations were observed. Injection of the dopamine receptor antagonist pimozide prevented the decrease in plasma PRL during the adaptation period, but had no effect on LH secretion. In pimozide-treated rats, U caused a 5-fold increase in the PRL concentration. This effect of U was inhibited by the serotonin receptor antagonist methysergide. The PRL response to 30 μg of histamine was similar in conscious and U-anaesthetized rats, whereas P anaesthesia caused a reduction in the response. It is concluded that the anaesthetics used here have no significant influence on the basal secretion of PRL and LH, and that the change in PRL secretion observed in non-adapted animals is not caused by the anaesthetic agents, but is due to the routine manipulation of the animals preceding induction of anaesthesia. We recommend that neuroendocrine experimentation be not initiated until 60 min after administration of anaesthetics.

Restricted access

Ulrich Knigge, Benedikte Thuesen, Anders Dejgaard, Birgit Svenstrup and Paul Bennett

Abstract

A stimulatory GH response to TRH and GnRH occurs frequently in patients with various pathological conditions, but is absent in normal subjects. We have previously shown that histamine induced a paradoxical GH response to TRH in normal men. Since gonadal steroids influence GH secretion, we investigated whether infusion of histamine might induce a GH response to combined administration of TRH (200 μg) and GnRH (100 μg) in 6 normal women during the early follicular and luteal phase of the same menstrual cycle and in 7 normal men. Histamine had no effect on basal GH secretion in men or in women during the two phases of the menstrual cycle. However, compared with saline, histamine induced a GH response to TRH/GnRH in men (GH peak: 5.5 ± 1.0 vs 1.4 ± 0.3 μg/l; p<0.01) and in women during the luteal phase (GH peak: 5.2 ± 1.6 vs 1.5 ± 0.4 μg/l; p<0.025), but not during the early follicular phase of the cycle (GH peak: 1.7 ± 0.5 vs 1.6 ± 0.3 μg/l). In luteal-phase women the GH response to TRH/GnRH correlated with the serum estradiol-17β level (GH area/E2: r=0.98; p<0.005) and the serum estrone level (GH area/E1: r=0.81; p<0.05). In men the GH response to TRH/GnRH did not correlate with estrogen or androgen levels. We conclude that high physiological levels of estrogens are pertinent to the activation of a histamine-induced GH response to TRH/GnRH in women, whereas the role of androgens and estrogens for the induction of the response in men seems more complex. Furthermore, the study indicates that histamine may increase the sensitivity of GH release to nonspecific stimuli.

Restricted access

Andreas Kjær, Ulrich Knigge, Steen Matzen and Jørgen Warberg

Kjær A, Knigge U, Matzen S, Warberg J. β-Adrenergic receptors are involved in histamine-induced secretion of proopiomelanocortin-derived peptides and prolactin in rats. Eur J Endocrinol 1995;132: 223–8. ISSN 0804–4643

The neurotransmitter histamine (HA) is involved in central regulation of secretion of prolactin (PRL) and the proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), β-endorphin (β-END) and α-melanocyte-stimulating hormone (α-MSH). The effect of HA on POMC-derived peptides and PRL release is, at least in part, indirect and may involve activation of catecholaminergic systems. Therefore, we investigated the effect of β-adrenergic receptor blockade on HA or HA agonist-induced release of ACTH, β-END, α-MSH and PRL. Central administration of HA, the H1-receptor agonist 2-thiazolylethylamine (2-TEA) or the H2-receptor agonist 4-methylhistamine (4-MeHA) stimulated the secretion of ACTH, β-END, α-MSH and PRL. Pretreatment with the β-adrenergic antagonist propranolol inhibited secretion of the POMC peptides in response to HA, 2-TEA or 4-MeHA. Propranonol only inhibited the PRL response to HA or 2-TEA, but had no effect on the PRL response to 4-MeHA. Administration of the β-receptor agonist isoproterenol stimulated ACTH, β-END, α-MSH and PRL two to five-fold. This effect was totally blocked by pretreatment with propranolol. We conclude that HA-induced secretion of POMC-derived peptides from the anterior and intermediate lobe of the pituitary gland and of PRL from the anterior lobe is, at least in part, mediated via catecholamines. β-Adrenergic receptors are involved in the mediation of the POMC response to H1- as well as H2-receptor activation, whereas β-receptors are involved only in the mediation of the PRL response to H1-receptor activation.

Andreas Kjær, Department of Medical Physiology, Division of Endocrinology and Metabolism, The Panum Institute (Building 12.3), University of Copenhagen, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark

Restricted access

Ulrich Knigge, Flemming W. Bach, Steen Matzen, Peter Bang and Jørgen Warberg

Abstract. In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and β-endorphin immunoreactivity 2.5-fold (P < 0.01). Gel filtration of plasma revealed two peaks of β-endorphin immunoreactivity corresponding to β-endorphin and β-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating β-endorphin immunoreactivity in control animals corresponded to β-endorphin. Central infusion of the H1-receptor agonist 2-thiazolylethylamine and of the H2-receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and β-endorphin immunoreactivity concentrations 2- and 3-fold, respectively (P < 0.01). Infused intracerebroventricularly, the H2-receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and β-endorphin immunoreactivity (P < 0.01), whereas the H1-receptor antagonist mepyramine inhibited the peptide responses by 70% (P < 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine-induced increase in plasma ACTH by 80% (P < 0.01) and plasma β-endorphin immunoreactivity by 45% (P < 0.05), whereas mepyramine or the other H1-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P < 0.05), but had no effect on the β-endorphin immunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin and β-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of β-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H2-receptors, whereas H 1-receptors appear to play a minor role.

Restricted access

Ulrich Knigge, Steen Matzen, Flemming W. Bach, Peter Bang and Jørgen Warberg

Abstract. Histamine, which acts as a neurotransmitter, stimulates the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin, and β-endorphin. Since stress affects the hypothalamic turn-over of neuronal histamine, we investigated the role of histaminergic neurons in the mediation of the stress-induced release of ACTH and β-endorphin immunoreactivity in male rats. In control animals histamine receptor antagonists had no effect on the release of ACTH or β-endorphin immunoreactivity. Restraint and ether stress increased plasma ACTH 3- and 2-fold, respectively. The responses were almost prevented by intracerebroventricular or intra-arterial infusion of the H2-receptor antagonists cimetidine and ranitidine. Infused intracerebroventricularly the H1-receptor antagonist mepyramine inhibited the ACTH response to restraint by 45% (P< 0.01), but had no effect on the response to ether. Infused intra-arterially the H1-receptor antagonists mepyramine or SKF-93944 had no effect. Restraint and ether stress increased plasma β-endorphin immunoreactivity 6- and 5-fold, respectively. Sephadex G-50 gel chromatography of plasma showed that the β-endorphin immunoreactivity in stressed rats coeluted with β-lipotropin and β-endorphin, whereas the immunoreactivity in control animals co-eluted almost exclusively with β-endorphin. The H2-receptor antagonists cimetidine and ranitidine infused intracerebroventricurlarly inhibited the responses of β-endorphin immunoreactivity to restraint and ether stress by 90 and 70%, respectively, whereas intra-arterial infusion of these antagonists inhibited the responses by only 50 and 60%, respectively. The H1-receptor antagonist mepyramine infused intracerebroventricularly inhibited the β-endorphin immunoreactivity response to restraint and ether stress by 40 and 25%, respectively, whereas intra-arterial infusion of mepyramine or the other H1-receptor antagonist SKF-93944 prevented the response to restraint stress, but had no effect on the response to ether stress. We suggest that hypothalamic histamine is involved in the mediation of the stress-induced release of the proopiomelanocortin-derived peptides ACTH, β-endorphin and β-lipotropin. The effect is mediated preferentially via H2-receptors, but H1-receptors may also play a role.