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Biomedical subjects

C Hagen

Publications and source records attributed to C Hagen.

At least 91 records · Page 5Linked to original sources

Plasma free and sulfoconjugated dopamine in man: relationship to sympathetic activity, adrenal function and meals.

Peripheral venous plasma free and sulfoconjugated catecholamines, dopamine (DA), noradrenaline (NA) and adrenaline (A) were measured in normal men (n = 6-7) during conditions significantly altering adrenal and sympathoadrenal function (influence of corticotropin, furosemide, hypoglycaemia and clonidine), after dopamine receptor blockade with metoclopramide and after meals. Median (range) basal plasma free DA concentration was 0.13 (0-0.72) nmol/l and median (range) basal plasma conjugated DA concentration was 15.16 (6.34-45.03) nmol/l. Meals increased plasma sulfoconjugated DA markedly from a median value of 14.97 nmol/l during fasting experiments to a median value of 33.01 nmol/l (p less than 0.05). Plasma free DA did not change in the meal experiments. No changes in plasma DA were observed after administration of corticotropin, furosemide, clonidine, and metoclopramide or during hypoglycaemia. The results suggest that plasma sulfoconjugated DA is derived at least in part from the gastrointestinal tract and not from the sympathoadrenomedullary system as hitherto proposed.

Adrenal Glands↗

Dopaminergic regulation of gonadotropin levels and pulsatility in normal women.

This study was done to define the concentration of dopamine (DA) that inhibits gonadotropin secretion and to study the effect of DA D-2 receptor blockade during the infusions. Normal women received 5-hour infusions of either glucose (n = 14) or DA at rates of 0.04 (n = 6), 0.4 (n = 6), and 4.0 micrograms/kg X minute (n = 9). After 3 hours, metoclopramide (MTC) was administered. Mean serum luteinizing hormone (LH) concentration declined during 0.4 (P less than 0.01) and 4.0 micrograms/kg X minute (P less than 0.05) infusion doses of DA. This effect of DA was not consistently (P greater than 0.05) antagonized by MTC. Six women received DA (4.0 micrograms/kg X minute) or glucose for 18 hours. After 17 hours, MTC was given. Blood samples were collected every 10 minutes during the last 8 hours. No significant effect on LH pulse frequency and pulse amplitude was observed (P greater than 0.05). A marked (P less than 0.01) rise in LH occurred after MTC administration. The authors conclude that (1) physiologic doses of DA may inhibit LH secretion with only little, if any, effect on the pulsatile release; and (2) low-affinity DA receptors responsive to DA D-2 antagonists may regulate LH secretion.

Adult↗

Pituitary-thyroid function and thyrotropin, prolactin and growth hormone responses to TRH in patients with chronic alcoholism.

Basal plasma concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), free T4 index (TF4I), free T3 index (FT3I) reverse T3, 3,3',5-triiodothyronine (rT3), resin T3 uptake (TR3U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T3 and rT3 plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT3U levels, while those without cirrhosis had increased RT3U and normal TBG levels. Plasma concentrations of basal as well as TRH-stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T3 levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease.

Adult↗

Increased dopaminergic activity inhibits basal and metoclopramide-stimulated prolactin and thyrotropin secretion.

The influence of physiological to pharmacological doses of dopamine (DA) on basal and metoclopramide (MTC)-stimulated PRL and TSH secretion was studied in 11 regularly menstruating women between days 3 and 8 of the cycle. In groups of 6, the women received 5-h infusions of either 5% glucose or DA in a solution of 5% glucose at a rate of 12-16 ml/h, adjusted according to weight. Infusion rates of DA were 0.04 microgram/kg . min (low), 0.4 microgram/kg . min (medium), and 4.0 micrograms/kg . min (high). After 3 h of infusion, 10 mg MTC were given iv. Blood samples were collected every 15 min from 1 h before to 2 h after the infusion, for a total of 8 h, for measurements of PRL and TSH. The mean serum PRL concentrations declined significantly (P less than 0.05) during DA infusions to nadir values of 62 +/- 5% (+/- SEM; low), 43 +/- 3% (medium), and 43 +/- 6% (high) of the basal levels, whereas basal TSH levels declined significantly, to 64 +/- 5% of basal levels (P less than 0.05), during both the medium and high dose DA infusions. On paired comparisons, the hormone responses to MTC were lower (P less than 0.05) during the infusion of high dose DA (PRL, 2286 +/- 495% vs. 891 +/- 328%; TSH, 100 +/- 43% vs. 60 +/- 15%), but were not changed when MTC was given during the low and medium doses of DA. A rebound phenomenon was found for PRL (P less than 0.05) after the medium and high doses of DA and for TSH (P less than 0.05) after the high dose. These results indicate that doses of DA considered physiological inhibit PRL and TSH secretion and larger doses inhibit their responses to the DA antagonist MTC.

Adult↗

Prolonged dopamine receptor blockade in normoprolactinemic amenorrhea: a double-blind placebo study.

Patients with functional amenorrhea may have a raised central dopaminergic activity, leading to inhibition of pituitary-ovarian function. In a double-blind placebo trial, ten patients with amenorrhea received metoclopramide (MTC) orally in daily doses from 20 to 7.5 mg in a sequential form for 10 weeks. Six patients received placebo. Serum levels for luteinizing hormone (P less than 0.02), follicle-stimulating hormone (P less than 0.05), and prolactin (P less than 0.001) increased significantly during MTC administration, and no (P greater than 0.05) hormonal changes occurred in the placebo group. Six patients observed vaginal bleedings during MTC administration but without postovulatory progesterone levels. Dopamine receptor blockade may activate the hypothalamic-pituitary axis of amenorrheic patients, although an ovulatory response is not achieved.

Adult↗

The effect of training on responses of beta-endorphin and other pituitary hormones to insulin-induced hypoglycemia.

We studied whether the previously reported intensified beta-endorphin response to exercise after training might result from a training-induced general increase in anterior pituitary secretory capacity. Identical hypoglycemia was induced by insulin infusion in 7 untrained (VO2max 49 +/- 4 ml X (kg X min)-1, mean and SE) and 8 physically trained (VO2max 65 +/- 4 ml X (kg X min)-1) subjects. In response to hypoglycemia, levels of beta-endorphin and prolactin immunoreactivity in serum increased similarly in trained (from 41 +/- 2 pg X ml-1 and 6 +/- 1 pg X ml-1 before hypoglycemia to 103 +/- 11 pg X ml-1 and 43 +/- 9 pg X ml-1 during recovery, P less than 0.05) and untrained (from 35 +/- 7 pg X ml-1 and 7 +/- 2 pg X ml-1 to 113 +/- 18 pg X ml-1 and 31 +/- 8 pg X ml-1, P less than 0.05) subjects. Growth hormone (GH) was higher 90 min after glucose nadir in trained (61 +/- 13 mU X l-1) than in untrained (25 +/- 6 mU X l-1) subjects (P less than 0.05). Levels of thyrotropin (TSH) changed in neither of the groups. It is concluded that, in contrast to what has been formerly proposed, training does not result in a general increase in secretory capacity of the anterior pituitary gland. TSH responds to hypoglycemia neither in trained nor in untrained subjects. Finally, differences in beta-endorphin responses to exercise between trained and untrained subjects cannot be ascribed to differences in responsiveness to hypoglycemia.

Adult↗

The distribution of liver metastases from colonic cancer. A quantitative postmortem study.

54 livers of patients with colonic cancer were investigated in a postmortem study. 26 livers contained metastases from colon carcinoma. Assessment of the number, size and location of metastases was made. The possible interdependence of the site of the colonic primary and the location of its secondaries in the liver was examined. Results suggest an approximately homogeneous distribution of metastases from colonic cancer in the hepatic parenchyma, irrespective of the location of the primary tumour.

Colonic Neoplasms↗

Gonadotropin secretion before and during acute and chronic dopamine-receptor blockade in insulin-dependent diabetic patients with amenorrhea.

The dopaminergic influence on luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) was studied in 12 diabetic patients with amenorrhea (DMAM) and in 10 normal menstruating diabetic patients (DM). DMAM patients had a reduction in LH pulsatility (P less than 0.05) and basal LH levels (P less than 0.02), compared with DM patients, whereas they had an LH and FSH response to intravenous metoclopramide (MTC) at 30, 45, and 60 minutes and at 30 minutes, respectively (P less than 0.05). Basal (P less than 0.05) and MTC-stimulated (P less than 0.05) PRL levels were lower in DMAM than in DM patients. Serum PRL and FSH increased significantly (P less than 0.02) in six DMAM patients during 10 weeks of oral MTC administration, whereas no significant (P greater than 0.05) alterations occurred in serum LH and estradiol levels. These data point toward increased dopaminergic activity in DMAM patients.

Adolescent↗

Autoantibodies in sera from patients with multiple sclerosis directed against antigenic determinants in pituitary growth hormone-producing cells and in structures containing vasopressin/oxytocin.

We have reported previously that autoantibodies in sera from patients with multiple sclerosis (MS) were reactive with rat brain, including pituitary, and with swine pituitary in areas thought to contain peptides of the somatotropin family and/or vasopressin/oxytocin. We have now tested the same patient sera for their specificity to antigenic determinants which are common to animal and human peptides. Localization of the binding sites of the MS sera was demonstrated in rat pituitaries and brains using the double immunofluorescence staining method, employing anti-bovine somatotropin (STH), anti-ovine prolactin (PRL), anti-neurophysin I and II, anti-somatostatin, and anti-vasopressin as reference antibodies. In the pituitary, the positive MS sera reacted specifically with cells which were also reactive with anti-bSTH. In the brain, positivity of MS sera was mainly localized in structures reactive with anti-neurophysin I and II and anti-vasopressin. Absorption experiments, immunocytochemical model assays, and radioimmunoassays, however, did not show specific binding of the MS sera to any of the above-mentioned peptides. Therefore, while these data present additional evidence on the localization of the immunocytochemical reaction sites of the MS autoantibodies, they do not enable us to identify the specificity of these antibodies.

Animals↗

Serum sex hormone concentrations in insulin dependent diabetic women with and without amenorrhoea.

Abnormal steroid secretion may contribute to anovulation in insulin dependent diabetic patients with amenorrhoea. We have measured serum sex hormone-binding globulin (SHBG) and free and bound oestrogen and androgen levels in 17 such patients. As controls we included 17 patients with insulin dependent diabetes mellitus and normal menstrual cycles, 21 regularly menstruating normal women (both sampled during early follicular phase), and 23 non-diabetic patients with amenorrhoea. The diabetic patients with normal cycles had significantly higher serum concentrations of delta 4-androstenedione and testosterone than the normal women (P less than 0.01). The amenorrhoeic diabetics in contrast had significantly lower serum concentrations of SHBG, 5 alpha-dihydrotestosterone and free and total oestradiol-17 beta than either group of menstruating women (P less than 0.05), and significantly lower concentrations of delta 4-androstenedione (P less than 0.01), dehydroepiandrosterone sulphate (P less than 0.01), testosterone (P less than 0.01), and oestrone (P less than 0.05), than the cycling diabetics. The two amenorrhoeic groups had similar free and bound sex hormone concentrations except that delta 4-androstenedione levels were significantly lower in the diabetics (P less than 0.01). We conclude that the low sex hormone levels in diabetic women with amenorrhea may be due to suppression of the hypothalamic-pituitary axis in view of the impaired LH secretion found in these patients and that excess androgen secretion seems not to be of aetiological importance in amenorrhea related to diabetes mellitus. The decreased steroid levels in amenorrheic diabetics is due to their suppressed ovarian function while the increased androgen levels in diabetics with regular cycles are probably of ovarian origin.

Adolescent↗

Abnormal conjugated dopamine levels in patients with normoprolactinaemic amenorrhoea and in insulin-dependent diabetic patients.

We determined the circulating dopamine levels in 17 patients with insulin-dependent diabetes mellitus (IDDM), of whom eight had amenorrhoea (DM-AM) and nine were normally menstruating (DM). Seven non-diabetic women with normoprolactinaemic, normogonadotrophic secondary amenorrhoea (AM) and nine normally menstruating women (controls) were studied. In all subjects basal blood concentrations of free dopamine (f-DA), conjugated dopamine (c-DA), epinephrine (E), norepinephrine (NE), prolactin (PRL), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and oestradiol-17 beta were determined and all subjects, except for three AM patients, had a Metoclopramide test performed for measurements of f-DA, c-DA, PRL, LH and TSH. Plasma c-DA was significantly (p less than 0.05) increased in patients with amenorrhoea compared to the respective control groups. In diabetic patients c-DA levels were significantly (p less than 0.05) lower compared to controls. The ratio between basal f-DA and c-DA concentrations was significantly (p less than 0.01) higher in diabetic patients compared with non-diabetic patients. After Metoclopramide stimulation DM-AM patients showed a significant (p less than 0.05) rise in c-DA, whereas this was not seen in other groups. DM-AM patients had significantly (p less than 0.05) lower basal PRL and LH levels than DM patients and controls. In addition DM-AM patients had a significantly (p less than 0.05) lower PRL response to Metoclopramide compared with DM patients. There were no significant correlations between catecholamines and basal as well as Metoclopramide stimulated pituitary hormones. This study suggests that the abnormal pituitary hormone secretion in patients with amenorrhoea may in part be caused by an increased dopaminergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence of altered dopaminergic modulation of Prl, LH, FSH, GH and TSH secretion during chronic partial dopamine receptor blockade in normal women.

In order to study the influence of chronic, partial dopaminergic blockade on pituitary secretion of Prl, TSH, GH, LH and FSH, 8 normally menstruating women were given metoclopramide (MTC, Primperan ) 7.5 mg daily for 4 weeks. Based on weekly measurements of progesterone, all cycles were ovulatory. Prior to and after 4 weeks of drug administration serial measurements of basal hormone levels as well as the acute alterations after 10 mg of MTC iv were assessed during the early follicular phase. Chronic MTC administration significantly increased serum Prl (P less than 0.02), reduced basal levels of LH (P less than 0.02), whereas basal serum concentrations of TSH, GH and FSH were not changed. Before chronic administration iv MTC evoked significant increments in serum Prl (P less than 0.001), TSH (P less than 0.001) and GH (P less than 0.005). The acute TSH increments were significantly (P less than 0.02) diminished after 4 weeks of treatment. The influence of chronic MTC administration on serum LH and TSH levels may be the result of a competitive effect of a stimulatory influence of the dopamine receptor blocker and an opposing inhibitory influence of an increased hypothalamic dopamine activity, evoked by the MTC induced hyperprolactinaemia. Our data favour that the latter mechanism is dominating in normal women, during chronic administration of a low dose of MTC.

Adult↗

Evidence of altered dopaminergic modulation of Prl, LH and TSH secretion in patients with normoprolactinaemic amenorrhoea.

Basal plasma concentrations of Prl, LH, FSH, GH, TSH, T3, T4, resin T3 uptake ( RT3U ), and oestradiol as well as hormone responses to iv metoclopramide (MTC) were investigated in 16 consecutive patients with normoprolactinaemic, normogonadotrophic amenorrhoea. The control group consisted of 17 normal menstruating women between day 3 and 6 of the menstrual cycle. The mean age of the amenorrhoeic patients was 24.0 years (range 19 to 34) and the mean duration of amenorrhoea was 31 months (range 12 to 60). Amenorrhoeic patients had significantly (P less than 0.05) lower basal levels of LH, oestradiol and RT3U , whereas other hormone levels were similar in the two groups. Plasma Prl and TSH concentrations rose significantly (P less than 0.05) after the administration of MTC in the two groups. A significant positive correlation (r = 0.69 P less than 0.01) was found between the TSH response to MTC and basal TSH levels in controls, but not in amenorrhoeic patients. Plasma LH levels increased significantly (P less than 0.05) in amenorrhoeic patients, but not in controls. The Prl and TSH responses to MTC were significantly (P less than 0.001) lower in amenorrhoeic patients than in normal women. In amenorrhoeic patients none of the hormonal parameters correlated significantly (P greater than 0.05) with the percentage of ideal body weight. It is concluded that the hormonal changes in amenorrhoeic patients may in part be caused by a raised dopaminergic activity leading to a depression of central ovulatory mechanisms.

Adult↗

Possible altered dopaminergic modulation of pituitary function in normal-menstruating women with insulin dependent diabetes mellitus (IDDM).

In order to assess whether a possible altered dopamine activity in normal-menstruating diabetic patients may influence the pituitary hormone secretion we have measured the basal serum concentrations of Prl, LH and FSH in 28 patients with insulin dependent diabetes mellitus (IDDM) and in 55 normal-menstruating women at day 3 to 6 of the menstrual cycle. In addition basal levels of oestradiol-17 beta, TSH, thyroxine (T4), triiodothyronine (T3) and resin-T3 uptake (RT3U) were determined in 17 patients with IDDM and in 17 controls. The responses of FSH, LH, Prl, GH and TSH to metoclopramide (MTC) administration (10 mg iv) were studied in 17 patients and 17 controls. In 10 patients with IDDM and 8 controls the short-term variations in pituitary hormones and blood glucose concentration were evaluated. Patients with IDDM had significantly lower basal levels of Prl (P less than 0.01) and TSH (P less than 0.05) and significantly (P less than 0.05) higher basal levels of GH than normal women. No significant (P greater than 0.05) differences were found regarding basal serum concentrations of FSH, LH, oestradiol, T4, T3 and RT3U. During the 3 h period the mean coefficient of variation of Prl, FSH, LH and GH was not significantly (P greater than 0.05) different between diabetic patients and controls. Both groups responded significantly (P less than 0.01) in Prl and TSH to MTC but the TSH response was significantly (P less than 0.05) lower in patients with IDDM. The Prl response to MTC was not significantly (P greater than 0.05) different within the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glucose tolerance and B cell function in chronic alcoholism: its relation to hepatic histology and exocrine pancreatic function.

Glucose tolerance and B cell function were assessed in 30 consecutive chronic alcoholic patients without overt diabetes mellitus. Plasma glucose, insulin, and C peptide concentrations were measured during an oral glucose tolerance test. All patients underwent a liver biopsy and an exocrine pancreatic function test (Lundh test). Compared with the controls, the three groups of alcoholic patients (those with histologically normal livers, n = 12; those with steatosis, n = 10; and those with cirrhosis, n = 8) all had a two-fold increase in plasma concentrations of insulin as well as C peptide in the fasting state, despite normal fasting levels of glucose. After oral glucose all groups of patients had elevated plasma levels of glucose, insulin, and C peptide compared with the controls. The C peptide/insulin ratio was similar to that in the controls in all groups of alcoholics. Patients with decreased exocrine pancreatic function (n = 7) had a significantly lower insulin and C peptide response to glucose than the patients with normal exocrine pancreatic function. It is concluded that (1) chronic alcoholics even with histologically normal livers have endogenous insulin resistance, and (2) associated damage to the exocrine pancreas is more common than previously recognized and decompensation of B cell function could be demonstrated in patients with decreased exocrine pancreatic secretion.

Adolescent↗

Autoantibodies against pituitary peptides in sera from patients with multiple sclerosis.

Autoantibodies against pituitary peptides were demonstrated in sera from multiple sclerosis (MS) patients. Ten patients with lupus erythematosus disseminatus (SLE) and 97 healthy blood donors served as controls. The sera were used as primary antibodies in the indirect immuno-enzyme cytochemical (IEC) method, with fixed, paraffin-embedded rat brains and rat and hog pituitaries as antigen substrates. Eleven of the 33 MS sera reacted with peptides in the neural lobe/hypothalamic nuclei or distal lobe. The MS had a significantly higher incidence of peptide antibodies than sera from controls (11/33 vs 9/97). The mean antibody titers were significantly different (1577 vs 333). Comparison with rabbit reference antibodies specific to each of the 6 distal lobe hormones showed that the 9 distal lobe-positive MS sera reacted with cells harboring peptides of the somatotropin family. The presence of peptide autoantibodies was not related to clinical status or medical treatment. No antibodies against pituitary peptides were found in the SLE sera. One of the 11 positive MS sera showed antibodies against gastric parietal cells. None of the 11 sera showed antibodies against muscle, mitochondria, thyroid, adrenal, or parotid antigens. We propose that in a proportion of patients with MS, these autoantibodies might be involved in the demyelinization process by interfering with the peptide/receptor interplay, thus placing MS as a disease in analogy with myasthenia gravis. Alternatively, these autoantibodies might be involved in the altered immunoregulation of MS or be secondary to the disease.

Adult↗