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Biomedical subjects

A Kjaer

Publications and source records attributed to A Kjaer.

At least 73 records · Page 4Linked to original sources
PubMed1993

Permissive, mediating and potentiating effects of vasopressin in the ACTH and beta-endorphin response to histamine and restraint stress.

We investigated in conscious, male rats (1) whether the role of arginine-vasopressin (AVP) in histamine (HA)- and/or restraint stress-induced stimulation of ACTH and beta-endorphin (beta-END) secretion is mediating and/or permissive and (2) whether AVP possesses a potentiating effect on HA- or stress-induced release of ACTH and beta-END. Administration of a specific V1 receptor agonist stimulated ACTH and beta-END secretion dose-dependently while a V2 receptor agonist had no stimulating effect. ACTH and beta-END secretion was stimulated 2- to 3-fold by intracerebroventricular (i.c.v.) infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited approximately 80% by immunoneutralization of endogenous AVP using a specific AVP antiserum. When the 'AVP tone' was restored in immunoneutralized animals by administration of the specific AVP V1 receptor agonist, which was not bound by the AVP antiserum and had no ACTH and beta-END-releasing effect in the dose used, the ACTH and beta-END response to HA or restraint stress was almost completely reestablished. The specific AVP V2 receptor agonist, which was not bound by the AVP antiserum, reestablished only in part the response of ACTH and beta-END to HA or restraint stress in immunoneutralized animals. AVP administered in doses which had no or minimal ACTH or beta-END releasing effect in itself enhanced the ACTH or beta-END response to submaximal stimulation with HA or restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Insulin/hypoglycemia-induced adrenocorticotropin and beta-endorphin release: involvement of hypothalamic histaminergic neurons.

We have previously found that histamine (HA) is involved in the mediation of restraint- and ether stress-induced release of the POMC-derived peptides ACTH and beta-endorphin (beta-END). In the present study we investigated the possible involvement of hypothalamic histaminergic neurons in the mediation of insulin/hypoglycemia-induced release of ACTH and beta-END in conscious male rats. To do so, hypoglycemia stress was performed during 1) inhibition of HA synthesis, 2) activation of inhibitory presynaptic HA H3-auto-receptors, or 3) blockade of postsynaptic HA H1- or H2-receptors. Hypoglycemia (plasma glucose, 2.2 +/- 0.3 nmol) induced by insulin (3 IU/kg, ip) caused a 3- to 5-fold increase in the plasma concentrations of ACTH and beta-END. A negative exponential correlation was found between the plasma glucose concentration and the ACTH and beta-END levels. Pretreatment of the animals with the HA synthesis inhibitor alpha-fluoromethylhistidine (1.0 mumol) intracerebroventricularly (icv) in a lateral ventricle, inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 60%. When administered ip (100 mumol/kg), the synthesis inhibitor decreased the beta-END response 50%, but did not affect ACTH secretion significantly. Pretreatment of the rats with the H3-receptor agonist R(alpha)methylhistamine (50 mumol/kg, ip, twice) inhibited the secretory responses of ACTH and beta-END to insulin/hypoglycemia by 60-80%. This inhibitory effect of R(alpha)methylhistamine was reversed by prior administration of the specific H3-receptor antagonist thioperamide. Administration of the H1-antagonists mepyramine and cetirizine dose-dependently inhibited the ACTH and beta-END responses to insulin/hypoglycemia, with the highest dose (mepyramine, 350 nmol, icv; cetirizine, 40 mumol/kg, ip) inhibiting the response by 80-100%. The H1-antagonist SKF-93944 (226 nmol, icv) inhibited the ACTH response, but had no effect on the beta-END response. Administration of the H2-antagonists cimetidine (400 nmol, icv) and ranitidine (400 nmol, icv) inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 50-80%. We conclude that histaminergic neurons are involved in the mediation of the insulin/hypoglycemia-induced release of ACTH and beta-END and that the effect is mediated via activation of primarily postsynaptic H1-receptors and, to a lesser extent, H2-receptors.

Adrenocorticotropic Hormone↗
PubMed1993

Vasopressin as a neuroendocrine regulator of anterior pituitary hormone secretion.

Secretion of the anterior pituitary hormones adrenocorticotropin (ACTH), beta-endorphin and prolactin (PRL) is complex and involves a variety of factors. This review focuses on the involvement of arginine-vasopressin (AVP) in neuroendocrine regulation of these anterior pituitary hormones with special reference to receptor involvement, mode of action and origin of AVP. Arginine-vasopressin may act via at least two types of receptors: V1- and V2-receptors, where the pituitary V1-receptor is designated V1b. The mode of action of AVP may be mediating, i.e. anterior pituitary hormone secretion is transmitted via release of AVP, or the mode of action may be permissive, i.e. the presence of AVP at a low and constant level is required for anterior pituitary hormones to be stimulated. Under in vivo conditions, the AVP-induced release of ACTH and beta-endorphin is mainly mediated via activation of hypothalamic V1-receptors, which subsequently leads to the release of corticotropin-releasing hormone. Under in vitro conditions, the AVP-stimulated release of ACTH and beta-endorphin is mediated via pituitary V1b-receptors. The mode of action of AVP in the ACTH and beta-endorphin response to stress and to histamine, which is involved in stress-induced secretion of anterior pituitary hormones, is mediating (utilizing V1-receptors) as well as permissive (utilizing mainly V1-but also V2-receptors). The AVP-induced release of PRL under in vivo conditions is conveyed mainly via activation of V1-receptors but V2-receptors and probably additional receptor(s) may also play a role.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Histamine- and stress-induced secretion of ACTH and beta-endorphin: involvement of corticotropin-releasing hormone and vasopressin.

Histamine (HA) stimulates the release of the pro-opiomelanocortin (POMC)-derived peptides ACTH, beta-endorphin (beta-END), beta-lipotropin and alpha-melanocyte-stimulating hormone, and HA is involved in the mediation of the stress-induced release of these peptides. The effect of HA is indirect and may involve the hypothalamic regulating factors, corticotropin-releasing hormone (CRH) and/or arginine-vasopressin (AVP). We studied the effect of immunoneutralization with specific antisera against CRH or AVP on the response of ACTH and beta-END to HA, restraint stress, CRH, AVP or a posterior pituitary extract in male rats. Intracerebroventricular infusion of HA (34-540 nmol) increased the plasma levels of ACTH and beta-END immunoreactivity (beta-ENDir) in a dose-dependent manner. Pretreatment with antiserum to CRH or AVP prevented the ACTH response to 270 nmol HA and inhibited the beta-ENDir response by 30-60%. One to five minutes of restraint stress caused an increase in the plasma levels of ACTH and beta-ENDir. The increase was dependent on the duration of stress exposure. Pretreatment with CRH antiserum abolished the ACTH response to 5 min of restraint stress and inhibited the beta-ENDir response by 60%. Immunoneutralization with AVP antiserum had only half the inhibitory effect of that seen with CRH antiserum. CRH (100 pmol i.v.) increased the plasma levels of ACTH and beta-ENDir. This effect was abolished by pretreatment with CRH antiserum, whereas pretreatment with AVP antiserum prevented the CRH-induced ACTH release and inhibited the beta-ENDir response by 50%. AVP (24-800 pmol i.v.) stimulated ACTH and beta-ENDir in a dose-dependent manner. CRH and AVP antisera each prevented the effect of AVP (800 pmol) on ACTH secretion, whereas the beta-ENDir response to AVP was only inhibited by about 60% by the antisera. An extract of the posterior pituitary gland administered in a dose corresponding to 0.15 or 0.5 pituitary equivalents had no effect on ACTH secretion, while 1.0 pituitary equivalent increased the ACTH concentration in plasma. This effect was abolished by AVP antiserum. The posterior pituitary extract caused a dose-dependent rise in plasma beta-ENDir which might be due to an unavoidable contamination of the posterior pituitary extract by a small amount of beta-END from the intermediate lobe. Consistent with this view, AVP antiserum had no effect on the rise in the plasma concentration of beta-ENDir following administration of the posterior pituitary extract.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Histamine H1 and H2 receptor activation stimulates ACTH and beta-endorphin secretion by increasing corticotropin-releasing hormone in the hypophyseal portal blood.

Histamine (HA) stimulates the release of adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-END) via activation of central postsynaptic H1 or H2 receptors. The effect of HA is indirect and may involve the hypothalamic regulating factors corticotropin-releasing hormone (CRH), arginine vasopressin, or oxytocin (OT). We studied the effect of specific HA H1 or H2 receptor agonists on the concentration of CRH and OT in hypophyseal portal blood in urethane-anesthetized male rats. In addition we investigated the effect of the agonists on ACTH and beta-END immunoreactivity in peripheral plasma in conscious male rats pretreated with antiserum to CRH. Intracerebroventricular administration of the H1 receptor agonist 2-thiazolylethylamine (2-TEA) or the H2 receptor agonist 4-methylhistamine (4-MeHA) increased the CRH concentration in pituitary portal blood by 80-90% when compared to preinfusion levels (p < 0.05). Central infusion of saline had no effect. The level of OT in the pituitary portal blood was not affected by 2-TEA or 4-MeHA when compared to saline-treated rats. Intracerebroventricular infusion of 2-TEA or 4-MeHA increased the ACTH concentration in peripheral plasma 3- or 4-fold, respectively (p < 0.01). Pretreatment with a specific CRH antiserum (abCRH) inhibited the responses by 50 and 70%, respectively (p < 0.01). Intracerebroventricular administration of 2-TEA or 4-MeHA increased the beta-END immunoreactivity in peripheral plasma 3- or 2-fold, respectively (p < 0.01). These effects were inhibited by 80-90%, when rats were pretreated with abCRH (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Mediation of the stress-induced prolactin release by hypothalamic histaminergic neurons and the possible involvement of vasopressin in this response.

We investigated the role of histamine (HA) in the neuroendocrine regulation of PRL secretion in conscious male rats. Blood samples were obtained by decapitation of the animals at 0 min. Intracerebroventricular infusion of HA (34-540 nmol at -15 min) stimulated PRL secretion dose dependently with an ED50 of approximately 135 nmol. Inhibition of neuronal HA synthesis by the specific histidine decarboxylase-inhibitor (S)alpha-fluoro-methylhistidine (alpha FMH; 100 mumol/kg ip at -6 h or 400 mumol/kg ip at -20 h and -6 h) caused a 50% reduction (P less than 0.01) in the PRL response to 5 min of restraint stress. Inhibition of neuronal HA metabolism by the specific histamine-methyltransferase-inhibitor SKF-91488 (400 and 800 nmol icv at -20 min) augmented the restraint stress-induced PRL release 26% and 37%, respectively (P less than 0.05). The two enzyme inhibitors had no or only modest effect on the basal PRL secretion. Pretreatment with a specific antiserum (0.5 ml) to arginine vasopressin (AVP) or an AVP antagonist (25 nmol) administered iv at -20 min inhibited the PRL response to HA (270 nmol icv) 80% and 45%, respectively (P less than 0.01) and inhibited the PRL response to restraint stress 70% (P less than 0.01). In contrast, pretreatment with a specific oxytocin (OT) antagonist (50 nmol) had no effect on the HA- or stress-induced PRL release. The AVP antiserum showed less than 0.0003% cross-reactivity with OT, and radiolabeled OT did not bind to serial dilutions of plasma from rats treated with the AVP antiserum. The AVP antiserum or the AVP antagonist almost prevented the PRL release induced by iv infusion of 800 pmol AVP or a posterior pituitary extract. Infusion of AVP (24-800 pmol iv at -15 min) stimulated PRL secretion dose dependently. However, the dose of AVP (800 pmol) required to induce an increase in plasma PRL similar to that obtained by HA-stimulation, led to a rise in plasma AVP which was approximately 1000-fold higher than that induced by HA, which increased plasma AVP 2-fold. Restraint stress had no effect on the plasma AVP level. We conclude that neuronal HA participates in the mediation of the PRL response to stress and that the stress- and HA-induced release of PRL may involve AVP, whereas an involvement of OT seems unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Central activin administration modulates corticotropin-releasing hormone and adrenocorticotropin secretion.

A broad and diffuse neuronal network conveys information reflecting the state of the internal and external environment to the neurosecretory hypothalamus. Recently, we identified an inhibin-beta A- (I beta A) immunoreactive terminal field within the CRF-rich portion of the dorsomedial paraventricular nucleus which originates from a cell group in the commissural portion of the nucleus of the solitary tract (NTS). The NTS receives baroreceptor input, somatosensory input via the spinosolitary tract, and sensory information from the oral, thoracic, and abdominal cavities and, thus, is positioned to serve as a primary relay for visceral sensory inputs to neurons critical to the function of the hypothalamic-pituitary-adrenal (HPA) axis. Although these NTS cells contain multiple putative transmitters, we present evidence that activin, an inhibin-beta A dimer, plays a modulatory role in HPA axis function via facilitation of CRF release. First, intraventricular injection of activin-A (0-3 nmol), but not the related inhibin heterodimer, evoked dose-related 1.7- to 2.8-fold elevations of circulating ACTH levels in male rats. Second, analysis of hypophysial-portal plasma after bilateral paraventricular nucleus microinfusion of activin-A revealed a dose-related facilitation of CRF secretion up to 4-fold above preinjection levels which was unaccompanied by changes in arginine vasopressin levels. Finally, activin-A also enhanced CRF secretion from neonatal hypothalamic cells in primary culture with an EC50 dose of approximately 0.25 nM. Overall, these observations provide evidence of both an anatomical and a pharmacological substrate for activin-mediated central modulation of HPA axis function.

Activins↗
PubMed1990

[Screening for cardiovascular risk factors in a large workplace].

A screening investigation was carried out in a large industry in the Copenhagen region and 1,472 of the employees were offered examination of blood cholesterol and measurement of blood pressure. At this examination the employees completed a one-page questionnaire about other cardiovascular risk factors. 45% of those invited participated in the investigation, the poorest participation was among women and the greatest among the male officials. On account of the limited number of female employees, the majority of results were only calculated for men. Over 1/3 of these had hypercholesteremia (greater than or equal to 7.0 mmol/l) and nearly 1/3 had, simultaneously, at least two cardiovascular risk factors in addition to age and male sex. Extensive occupational investigations under the auspices of WHO have demonstrated that energetic intervention at the place of work aimed at the cardiovascular risk factors can reduce the risk of development of coronary heart disease and death within a six-year follow-up period. It is therefore emphasized that similar interventions are very necessary also in Denmark.

Adult↗
PubMed1990

[Medical services on an inspection ship in the north Atlantic].

The Danish Naval Inspection Ships sail in the North Atlantic waters with a doctor on board. The object of this investigation was to illustrate the medical services on board and to elucidate the significance of various factors to predict seeking medical advice. During a period of three months, all of the medical services and certain basic factors were registered. The crew was interviewed about consumption of alcohol and tobacco, previous life at sea and family background. A total of 305 consultations were used by the crew of 72 men. This figure is five times the anticipated figure in general practice. Low rank and low age were predictors for frequent medical consultations. The diagnosis groups of traumata/injuries, dermatological conditions and disease in the nervous system or organs of sense were relatively overrepresented. A series of factors may possibly have influenced the pattern of seeking medical help so that this differs from general practice. It is concluded that the dangerous working environment and poor possibilities for good hygiene are important factors whereas the mental stress is of lesser significance.

Adult↗
PubMed1990

Metabolic changes during treatment with two different progestogens.

Two triphasic oral contraceptives containing the same amount of ethinyl estradiol in combination with gestodene or levonorgestrel were compared with respect to contraceptive effect, on lipid metabolism and coagulation. Serum concentrations of gestodene, levonorgestrel, ovarian and pituitary hormones, and sex hormone-binding globulin were measured. Thirty-five randomized into two groups receiving either of the preparations. Before treatment and in the third and sixth cycles, blood sample were drawn in the morning while subjects were still in bed to obtain basal conditions. The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects. Sex hormone-binding globulin was elevated twofold in the levonorgestrel group and threefold in the gestodene group. The gestodene concentration in serum varied more than the levonorgestrel concentration, but with correction for variations in sex hormone-binding globulin binding, less variability in gestodene and levonorgestrel concentrations were seen. High-density lipoprotein2 cholesterol decreased in the levonorgestrel group but was unchanged in the gestodene group, whereas apolipoprotein A1 increased in the gestodene group but not in the levonorgestrel group. Antithrombin III decreased in the gestodene group but was unchanged in levonorgestrel-treated women. Factor VII increased in both groups but more in the gestodene group. We conclude that gestodene has a positive influence on lipid metabolism, probably because of its lower androgenicity, and a slightly negative influence on coagulation. The latter, however, probably has no clinical relevance.

Adult↗
PubMed1990

Metabolic changes during the normal menstrual cycle: a longitudinal study.

The effect of sex hormones on lipid metabolism and coagulation during the menstrual cycle was studied in 37 women. Each woman had three samples drawn, corresponding to the follicular phase, midcycle, and the luteal phase. Basal conditions were obtained by taking samples in the morning while subjects were still in bed. No changes were found in lipids and lipoproteins during the menstrual cycle. Antithrombin III and factor VII of the coagulation system did not change throughout the cycle. Fibrinogen increased in the luteal phase, and all samples of fibrinogen correlated positively with progesterone concentration. This increase, therefore, could be a progesterogenic effect. In conclusion, these findings suggest that when studied optimally no changes in lipids and lipoproteins are found and that the day of blood samples is of minor importance, for instance, when used as a control in studies of oral contraceptives. For investigations on some coagulation parameters, the days of the cycle may be of importance.

Adult↗
PubMed1990

Clinical and hormonal effects of two contraceptives: correlation to serum concentrations of levonorgestrel and gestodene.

Two triphasic oral contraceptives containing gestodene (GES) (a new progestogen) and levonorgestrel (LNG) were compared with respect to contraceptive effect, cycle control, acceptability and side effects. The serum concentrations of ingested hormones were measured together with ovarian, pituitary, and some adrenal hormones, as well as sex hormone binding globulin (SHBG). The contraceptive effect and cycle control were good with both preparations, and there were only a few minor side effects. SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group. The GES concentration in serum varied more than the LNG concentration, but with correction for variations in SHBG binding, less variability in actual GES and LNG concentrations was seen. Serum levels of FSH, LH, estradiol and progesterone were all depressed with both preparations. The depression was more marked in the GES group, despite lower progestogen ingestion and similar serum concentrations. Equal decreases were found in testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) with both preparations.

Adult↗
PubMed1990

The prolactin releasing effect of histamine is unrelated to its vascular action.

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 mumol) 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.

Animals↗
PubMed1989

Lipid metabolism and coagulation of two contraceptives: correlation to serum concentrations of levonorgestrel and gestodene.

The effects of two triphasic oral contraceptives containing the same amount of ethinylestradiol (EE) in combination with levonorgestrel (LNG) or gestodene (GES), respectively, on lipid metabolism and coagulation were studied. Serum concentrations of GES and LNG were determined at the same time. Thirty-three healthy women were randomized into two groups receiving either of the preparations. Before treatment and in the 3rd and the 6th cycle, blood samples were drawn in the morning while subjects were still in bed to obtain basal conditions. HDL2-cholesterol decreased in the LNG group but was unchanged in the GES group, whereas apolipoprotein A1 increased in the GES but not in the LNG group. Antithrombin III decreased in the GES group but was unchanged in the LNG-treated women. Factor VII increased in both groups, but more in the GES group. It is concluded that GES has a positive influence on lipid metabolism, and has a slightly negative influence on coagulation but the latter is more likely to be without clinical relevance. The positive influence of GES compared to LNG on lipids is probably due to its lower androgenicity and not to differences in bioavailability.

Adult↗
PubMed1989

Lipid metabolism and coagulation during the normal menstrual cycle.

To examine the effects of sex-hormones on lipids, lipoproteins and coagulation in the normal menstrual cycle 37 women had blood samples taken early in the follicular phase (low estrogen) at the midcycle (high estrogen) and late in the luteal phase (high estrogen and high progesterone) under the best possible uniform and basal conditions. No significant changes (P greater than 0.05) in lipids and lipoproteins (including the HDL subfractions and apolipoproteins) were found throughout the menstrual cycle. In the coagulation system antithrombin III and factor VII did not change (P greater than 0.05). Fibrinogen, however, showed a significant (P less than 0.05) increase in the luteal phase compared to the follicular phase and midcycle. Fibrinogen showed a significant positive correlation (r = 0.2766; P less than 0.01) with progesterone, so the rise in fibrinogen in the luteal phase could be a progesterone effect. This longitudinal study performed on a large number of women under basal conditions showed that it seems of minor importance to define exact days of the cycle for analysing lipids and lipoproteins e.g. as controls in a study of lipid metabolism in women taking sex-hormones. For coagulation studies the cycle days may, however, be of importance.

Adult↗