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Biomedical subjects

E Haug

Publications and source records attributed to E Haug.

At least 109 records · Page 6Linked to original sources
PubMed1992

The lipoxygenase inhibitor nafazatrom inhibits stimulated prolactin secretion in cultured rat lactotrophs (GH4C1 cells).

Arachidonic acid metabolites are involved in the regulation of prolactin (PRL) secretion from rat lactotrophs (GH4C1 cells). Phospholipase A2 (PLA2) stimulated PRL secretion, while the PLA2 inhibitor quinacrine reduced both thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated PRL release. Hormonally stimulated PRL release was further increased in the presence of the cyclo-oxygenase inhibitor indomethacin. Nafazatrom, a lipoxygenase inhibitor, reduced stimulated PRL secretion regardless of the mechanism of stimulation [hormonally (VIP and TRH) or by increasing intracellular Ca2+ concentration by KCl or Bay-K and cAMP by forskolin]. None of the inhibitors used in this study had any effect either on the basal PRL secretion or on the production of cAMP. Lipoxygenase products seem to be involved in the regulation of PRL secretion, probably by affecting a late step in the signal transduction.

Animals↗
PubMed1992

Transgenic mice that develop pituitary tumors. A model for Cushing's disease.

Transgenic mice that developed adrenocorticotropic hormone (ACTH)-producing pituitary tumors were generated with the polyoma early region promotor linked to a cDNA encoding polyoma large T antigen (PyLT). Light microscopic examination of the pituitaries showed normal morphology at 4 months of age, either unremarkable morphology or microadenoma formation at 9 months of age, and up to 5 mm large adenomas in clinically ill transgenic mice at 13-16 months of age. At age 9 months, transgenic mice weighed significantly more than corresponding control mice, but they began wasting at approximately 1 year of age. The adrenal glands of these older PyLT-1 mice showed a weight increase and exhibited a medullary hyperplasia. Subcutaneous transplants of transgenic pituitary tumors to nontransgenic, immunocompetent mice resulted in tumors with a morphology and ACTH immunoreactivity similar to the primary tumor. The effects of hypercorticotropism were more enhanced and occurred with a shorter latency in the mice carrying transgene pituitary transplants than in the PyLT-1 transgenic mice themselves. Moreover, these transplanted mice showed a weight increase with an axial deposition pattern and hypertrophy of the adrenal cortex that resembled the findings in human Cushing's disease. Plasma ACTH levels were significantly increased in clinically ill transgenic mice and even higher levels were found in the transplant mice. Thus, both murine models should be useful for studying Cushing's disease.

Adrenal Glands↗
PubMed1991

Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells.

UNLABELLED: The causes of the "endothelial dysfunction" accompanying preeclampsia are unknown. Women with preeclampsia have a marked hyperlipidemia which reflects altered lipid metabolism. We asked if the hyperlipidemic sera of preeclamptic women could cause altered endothelial cell properties. Cultured endothelial cells were incubated with sera from women with preeclampsia (PE) or normal pregnancies as controls. Fifty PE-sera were tested and in 45 cases the endothelial cells acquired a large number of sudanophilic granules which by electron microscopy had lipid appearance. In 31 incubations with 31 individual control sera cellular lipid granules were observed in 4 cases. The cellular triglyceride content was increased to 153 +/- 30 compared to 48 +/- 10 micrograms/mg cell protein in the control cells. Furthermore, the endothelial release of prostacyclin, measured as 6-keto PGF1 alpha, was 8.8 +/- 0.6 ng/mg cell protein in cells incubated with PE-sera as compared to 40.3 +/- 6.4 ng/mg in the control cells. CONCLUSION: The hyperlipidemic sera from preeclamptic women induced triglyceride accumulation in cultured endothelial cells. This was accompanied by altered endothelial function as demonstrated by reduced prostacyclin release.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

[Determination of intact parathyroid hormone in patients with calcium metabolism disorders].

We have used an immunoradiometric assay (IRMA) to measure intact PTH. The serum-levels of PTH followed a log-normal distribution in a population of 85 healthy post-menopausal women, with a geometric mean of 1.9 pmol/l and a range of 0.8-6.1 pmol/l. The correlation between measurements performed using the IRMA and a radioimmunoassay which measured the C-terminal portion of the PTH molecule was 0.85. It was only the IRMA, however, that could measure subnormal values. Two of 27 patients with primary hyperparathyroidism had PTH-values in the upper reference interval. The rest of the patients had elevated levels. Patients with hypercalcemia due to malignancy had subnormal or low normal (less than 2.5 pmol/l) PTH values. Half of the patients with hypoparathyroidism had PTH below the limit of detection. Four subjects with familial hypercalciuric hypercalcemia had normal (3) or slightly elevated PTH-levels.

Adult↗
PubMed1991

Cholecalciferol metabolites attenuate cAMP production in rat thyroid cells (FRTL-5).

A rat thyroid cell line (FRTL-5) was used to study the effect of cholecalciferols on cAMP production. The active cholecalciferol metabolite, calcitriol, caused a reduction in basal and thyrotropin (TSH)-stimulated cAMP production. The inhibitory effects were demonstrated after 1 and 2 days, respectively. The maximum effect on both basal and TSH-stimulated cAMP production was observed after 3-4 days of treatment. The effect was detectable at 10(-10) and maximal at 10(-8) mol/l. Calcitriol was about 300 times more potent than calcidiol in attenuating cAMP production, whereas (24R)-hydroxycalcidiol in concentrations up to 3 x 10(-8) mol/l had no effect. After removal of added calcitriol the cAMP response to TSH returned to normal within 8 days. Calcitriol (10(-8) mol/l) also inhibited cell growth. Our results show that calcitriol at physiological concentrations inhibits both basal and TSH-stimulated cAMP production in rat thyroid cells. This indicates that calcitriol may modulate the effect of TSH on thyroid function and growth.

Adenylyl Cyclases↗
PubMed1991

Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia.

We report a patient with recurrent hypoglycemia most likely caused by a solitary fibrous tumor of the pleura. After removal of the tumor, hypoglycemia resolved. The bland histologic picture of this tumor is emphasized. Electron microscopic and immunohistochemical observations support its non-mesothelial derivation. In vitro studies demonstrated that the tumor tissue produced insulin-like growth factor I (IGF-I), and its role as the cause of hypoglycemia is discussed.

Aged↗
PubMed1991

Cardiac left ventricular function before and during early thyroxine treatment in severe hypothyroidism.

In some patients with severe hypothyroidism, thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even cured. Cardiac function in eight severely hypothyroid patients was studied by means of radionuclide ventriculography (RNV) at rest and during supine bicycle exercise before thyroxine treatment, and repeated during treatment before and after administration of 160 mg of oral verapamil. There was an exercise-induced fall in left ventricular ejection fraction (LVEF) in two patients before therapy, and in two additional subjects after 17 d on suboptimal doses of thyroxine. Verapamil attenuated the fall and induced a significant increase in LVEF during exercise (P less than 0.014). No abnormal regional cardiac wall movement (RWM) was observed. After 2 months of thyroxine treatment, LVEF increased significantly during exercise both before and after verapamil (P less than 0.012 and P less than 0.005). These findings are indicative of reversible coronary artery dysfunction. We recommend that, if feasible, thyroxine should be supplemented with verapamil during the early phase of treatment.

Adult↗
PubMed1991

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

In vivo and in vitro inhibition by ketoconazole of ACTH secretion from a human thymic carcinoid tumour.

We treated a patient with an ectopic ACTH-producing thymic carcinoid tumour with ketoconazole. The treatment decreased blood levels of ACTH and cortisol and relieved the patient's symptoms. Tumour explants secreted ACTH to the culture medium for at least 11 days. The tumour cells responded to high extracellular K+ concentration with increased ACTH secretion, whereas the hypothalamic ACTH-releasing hormone (CRH) and cortisol had no effect on ACTH secretion. Addition of ketoconazole to the culture medium decreased ACTH secretion showing that ketoconazole had a direct effect on the tumour cells.

Adrenocorticotropic Hormone↗
PubMed1991

Calcitriol receptors in rat thyroid follicular cells (FRTL-5).

The FRTL-5 cell line is widely used as a model for normal thyroid follicular cells. These cells have retained their ability to alter cAMP production, cell proliferation, iodine uptake, and thyroglobulin synthesis in response to thyrotropin. We have previously shown that calcitriol attenuated both basal and TSH stimulated cAMP production dose-dependently in FRTL-5 cells. Cytosol fractions (105,000 g, 60 min, 4 degrees C) prepared from FRTL-5 cell homogenates possessed calcitriol-binding components with a sedimentation coefficient of approximately 3.7 S in high salt (0.3 mol/l KCl) sucrose gradients (5-20%). At 4 degrees C, specific binding increased rapidly during the first 4 h and reached a plateau after 8 h. The specific binding (18 h, 4 degrees C) was maximal at a [3H]calcitriol concentration of approximately 0.5 nmol/l. Scatchard analysis of the binding data indicated one single class of high affinity binding sites with Kd = 105 +/- 2 pmol/l and Bmax = 38.5 +/- 4.7 pmol/g cytosol protein (mean +/- SD, N = 6). In conclusion, our results suggest that the FRTL-5 cells possess functional receptors for calcitriol with the same physicochemical properties as the receptors found in normal rat tissues.

Animals↗
PubMed1990

[Gonad function in men with alcoholic liver disease].

The connection between alcoholic liver disease and hypogonadism has long been recognized. In this study of 112 males admitted to a medical department, altogether 87 had alcoholic liver disease. Serum testosterone was depressed (less than 12 nmol/l) in 47 out of 51 (92%) patients with alcoholic liver cirrhosis and in 13 out of 36 (36%) with alcoholic fatty liver (p less than 0.001). Primary hypogonadism was found in 8% of the patients with alcoholic fatty liver and in 16% of the patients with alcoholic cirrhosis and secondary hypogonadism in 28% of the patients with fatty liver and in 76% of those with alcoholic cirrhosis. Serum sex hormone binding globulin (SHBG) was increased (greater than 40 nmol/l) in 65% of the patients with fatty liver and in 67% of the patients with alcoholic cirrhosis. Serum testosterone was significantly correlated to liver function tests Normotest (NT), bilirubin and albumin. In conclusion, hypogonadism is very common in men with alcoholic liver disease.

Adult↗
PubMed1990

The mechanisms by which vasoactive intestinal peptide (VIP) and thyrotropin releasing hormone (TRH) stimulate prolactin release from pituitary cells.

The effect of vasoactive intestinal peptide (VIP) on prolactin (PRL) secretion from pituitary cells is reviewed and compared to the effect of thyrotropin releasing hormone (TRH). These two peptides induced different secretion profiles from parafused lactotrophs in culture. TRH was found to increase PRL secretion within 4 s and induced a biphasic secretion pattern, while VIP induced a monophasic secretion pattern after a lag time of 45-60 s. The secretion profiles are compared to changes in adenylate cyclase activity, production of inositol polyphosphates, changes in intracellular calcium concentrations and changes in electrophysiological properties of the cell membrane.

Adenylyl Cyclases↗
PubMed1990

Stimulation with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression in polycystic ovarian syndrome.

Stimulation with human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was compared in 34 patients with polycystic ovarian syndrome after pituitary gonadotrope suppression with buserelin acetate. No differences were seen in the hormone parameters observed. Also, the duration of the stimulation period and the dose of gonadotropin used were the same. In both groups a multifollicular response was seen. Oocyte retrieval and in vitro fertilization resulted in identical ratios of mature to total oocytes and cleavage rates. Nine pregnancies occurred, four in the hMG group and five in the FSH group. Of the nine pregnancies, two were the result of transfer of frozen-thawed embryos in estradiol and progesterone substituted cycles.

Adult↗
PubMed1990

Serum levels of sex hormone binding globulin and oestradiol in patients with testicular cancer.

Serum testosterone (T), oestradiol (E-2) and sex hormone binding globulin (SHBG) were measured in 84 orchiectomised testicular cancer patients before further treatment and 4 to 6 and 12 to 15 months after therapy. Patients were divided into 3 groups according to treatment: Group 1: cisplatin-based chemotherapy (27 patients); Group 2: abdominal radiotherapy (32 patients); Group 3: no antiproliferative treatment (chemotherapy/radiotherapy) (25 patients). Between 4 and 6 months after antiproliferative treatment, particularly after chemotherapy, a reversible significant increase in E-2 and SHBG was observed. Patients without antiproliferative treatment showed no significant changes in their comparable hormone levels; 15% of all normal T values were associated with elevated levels of SHBG and E-2. Although the aetiology of these hormonal changes remains unknown, they may be related to the clinical symptoms of hypogonadism displayed by 10 to 30% of patients undergoing treatment for testicular cancer.

Adolescent↗
PubMed1990

The effects of secretin on prolactin, estradiol, vasoactive intestinal polypeptide, and somatostatin levels in women.

The effect of graded doses of intravenous secretin (0.5, 1.0, and 2.0 CU.kg-1.h-1) on serum prolactin and estradiol levels, as well as plasma vasoactive intestinal polypeptide and somatostatin levels was studied in 6 normally cycling and healthy women, and compared with the hormone levels obtained by a control infusion with physiologic saline (0.15 mol/l). A significant decrease in serum prolactin concentrations was found with increasing doses of secretin at steady-state levels of plasma secretin (+30 to +60 min). A significant negative correlation (p less than 0.007, r = -0.2764) existed between serum prolactin and plasma secretin concentrations at steady-state conditions. No effect of graded doses of secretin was observed on serum estradiol levels and plasma concentrations of vasoactive intestinal polypeptide and somatostatin. The results suggest a dose-related inhibitory effect of secretin on prolactin release in women.

Adult↗
PubMed1990

The source of cholesterol for progesterone synthesis in cultured preovulatory human granulosa cells.

There are three possible sources of cholesterol for immediate use in progesterone production by preovulatory human granulosa cells: follicular fluid high-density lipoprotein, de novo synthesis of cholesterol, and performed intracellular cholesteryl ester stores. In the present study these three alternatives were investigated. First, an in vitro model was established that mimics the preovulatory environment, including short-term cultures and use of autologous follicular fluid in the culture medium, instead of serum. Using this model it was found that the presence of high-density lipoprotein from follicular fluid in the culture medium did not affect the synthesis of progesterone by the granulosa cells. Next, addition of inhibitors of de novo sterol synthesis, like low-density lipoprotein, 25-OH cholesterol and compactin to the culture medium, did not reduce [14C]acetate incorporation into sterols and steroids by the cells. The sterol synthesis was accordingly interpreted to be at a low and therefore uninhibitable level. Finally, the content of free and esterified cholesterol in freshly isolated granulosa cells was found to be 50 +/- 7 and 52 +/- 13 pmol/mg cell protein, respectively. We suggest that neither follicular high-density lipoprotein nor endogenous synthesis is the immediate cholesterol source for the progesterone production in preovulatory human granulosa cells. However, granulosa cells have a large store of cholesteryl esters that may provide free cholesterol for the preovulatory progesterone production.

Aminoglutethimide↗