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Biomedical subjects

E Haug

Publications and source records attributed to E Haug.

At least 163 records · Page 9Linked to original sources
PubMed1985

Circadian rhythms in accessory sex gland function in the male rat.

Alterations in various parameters of accessory sex gland function were monitored during two separate 24 h periods in adult male rats, and compared to fluctuations in the circulating levels of testosterone, prolactin, corticosterone and LH. Bimodal circadian rhythms in ventral prostate prolactin binding, cytosolic oestrogen binding and seminal vesicle weight could be discerned which appeared to be related to a similar rhythmicity in circulating testosterone levels, but with a phase shift of 3 h. Prostatic membrane bound adenylyl cyclase activities (basal and hormone stimulated) and prostatein concentrations followed different patterns possibly correlated to other endocrine changes.

Adenylyl Cyclases↗
PubMed1985

The mechanism of 17 beta-estradiol uptake into prolactin-producing rat pituitary cells (GH3 cells) in culture.

Estrogens stimulate PRL synthesis in cultured GH3 cells, which are clonal strains derived from the rat pituitary gland. This model system was used to study the mechanism by which 17 beta-estradiol (E2) enters target cells. The cellular uptake of [3H]E2 was rapid at 37 C and reached half-maximal values within 10-15 sec. Maximal uptake was observed in less than 2 min at 37 C. The initial rates of E2 uptake were a linear function of the extracellular hormone concentration. The uptake of [3H]E2 in intact cells and the binding to cytosol studied at different temperatures resulted in linear Arrhenius plots, and the energies of activation were 39.0 and 33.5 kJ mol-1 degree-1, respectively. Purified GH3 cells membrane fractions, which showed specific binding sites for [3H]TRH, displayed the same maximal binding of [3H]E2 in the absence or presence of cold hormone. The amount of membrane-associated [3H]E2 increased linearly with temperature and extra-cellular hormone concentration. The effect of temperature on binding of E2 to membrane fractions occurred gradually without phase transitions and was not saturable. We suggest that the mechanism by which E2 is taken up by target cells at physiological temperature involves instantaneous dissolution in the cell membrane from where it diffuses passively into the cell. E2 binds thereafter to specific receptors in an energy-dependent step.

Animals↗
PubMed1985

Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells.

Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 X 10(-5) mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 X 10(-6) mol/l and 7 X 10(-6) mol/l, respectively. Maximum effect was obtained at 5 X 10(-5) mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by approximately 70 and approximately 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was approximately 1 X 10(-5) mol/l and the maximum effect (greater than 50%) was observed at 5 X 10(-5) mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The antiproliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug. In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.

Adenoma↗
PubMed1985

Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells.

The effects of bromocriptine, a dopamine (DA) agonist, on cell cycle distribution and cell morphology have been studied in a clonal strain of rat pituitary adenoma cells (GH3) which produce and secrete spontaneously both prolactin (Prl) and growth hormone (GH). DNA flow cytometry showed that bromocriptine caused a dose-dependent delay in cell cycle traverse concomitantly with a reduction in cellular growth rate. The lowest concentration of bromocriptine (5 X 10(-6) mol/l) significantly (P less than 0.05) increased the relative number of cells in the S phase and reduced the proportion of cells in the G1 phase. At higher concentrations (1 X 10(-5)-5 X 10(-5) mol/l) bromocriptine delayed cell cycle traverse through effects on cells in the S, G1 and G2 phases. These effects occurred already after 24 h of treatment. These results were supported by autoradiography of nuclear uptake of [3H]thymidine and by measurements of the number of cells arrested in metaphase after colcemide treatment (mitotic rate). Bromocriptine at 5 X 10(-5) mol/l altered profoundly GH3 cell structure inducing cell clustering and typical changes in mitochondrial and nuclear ultrastructures. Since Prl and GH production is a characteristic of cells in G1 phase, the inhibitory effect of the lowest antiproliferative concentration of bromocriptine (5 X 10(-6) mol/l) can only partly be explained by alterations in phase distribution. At the highest concentration of bromocriptine (5 X 10(-5) mol/l) hormone production and cell division are also inhibited due to general toxic effects as reflected by the ultrastructural changes.

Adenoma↗
PubMed1985

Short-term effects of prolactin on prostatic function in rats with lisuride-induced hypoprolactinaemia.

The effects of a single injection of ovine prolactin on prostatic function were monitored in intact, intact androgenized and castrated-androgenized rats rendered hypoprolactinaemic after 7 days of treatment with a potent dopamine agonist, lisuride. Hypoprolactinaemia was associated with reductions in ventral prostate weight, polyamine levels, lateral lobe zinc and the concentration of the ventral prostate protein prostatein, but an elevation in the level of cytosolic oestradiol binding. Whether these differences attained statistical significance depended on whether the animals were intact, intact-androgenized or castrated-androgenized. With the exception of ventral prostate weight and lateral lobe zinc concentrations, a single injection of prolactin restored or reversed these changes towards control levels within 12 h, which could not be explained by an indirect effect of the hormone on adrenal or testicular function. No effects of lisuride or prolactin were observed with regard to the content of fructose in the coagulating gland or in the degree of prolactin binding to prostatic membranes.

Androgen-Binding Protein↗
PubMed1985

Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma. Pharmacokinetics and effects on adrenal function.

A radio-immunoassay for the determination of the serum concentration of hydroxyprogesterone caproate (HPC) was established. After a single intramuscular injection of 1000 mg, the mean serum level reached its maximum (44-81 nmol/l) after 2-7 days. Patients on long-term adjuvant HPC treatment (consisting of 1000 mg daily for 5 days followed by 1000 mg every 2 weeks) presented peak hormone levels 2 weeks after commencing treatment. After a drop at 5 weeks, the mean serum level slowly increased again to 130 nmol/l after 25 weeks of treatment. Patients being treated with weekly injections had significantly higher serum levels than those treated every 2 weeks. Considerable inter-individual differences were observed. The serum concentrations of HPC measured in this study compare favorably with those previously found in patients treated with medroxyprogesterone acetate. The patients on adjuvant HPC showed no significant change in the levels of cortisol, dehydroepiandrosterone sulphate, androstenedione, or estrone during the first 25 weeks of treatment.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1984

Circulating concentrations of testosterone, luteinizing hormone and follicle stimulating hormone in male rats after inhalation of methanol.

Male mature rats were examined for alterations in circulating free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after inhalation of methanol vapour in a dynamic system for up to 6 weeks at doses ranging 200 ppm to 10,000 ppm. The most extensive effects were observed after exposure to 200 ppm of methanol for 6 weeks with serum testosterone concentrations being 32% of the controls. A significant change in LH concentration after exposure to 10,000 ppm of methanol for 6 weeks was also demonstrated. FSH remained unchanged throughout these experiments. Such exposure did not change the elimination rate of testosterone from blood which indicated effects on the testicular synthesis of testosterone.

Air Pollutants↗
PubMed1984

Vasoactive intestinal peptide causes a calcium-dependent stimulation of prolactin secretion in GH4C1 cells.

We have studied the effects of vasoactive intestinal peptide (VIP) on PRL secretion in a Bio-Gel column parafusion system containing rat pituitary tumour cells (GH4C1). A dose-dependent increase in PRL release was observed with half-maximal and maximal effect (2.1-fold) at 8 X 10(-8) and 5 X 10(-6) M, respectively. The PRL-stimulatory effect of VIP was instantaneous and maintained during the parafusion experiments (up to 60 min). On a molar basis VIP was always less effective than thyroliberin (THR), and the maximum stimulation of PRL release obtained with TRH was 1.2-3.0-fold higher (n = 12) than the maximum effect seen after VIP administration. The PRL-releasing effects of VIP, THR and high extracellular K+ were almost completely abolished in the presence of two inhibitors of voltage-sensitive Ca2+ channels, CoCl2 (10(-3) M) and verapamil (10(-4) M). In Ca2+-free buffer VIP, TRH and high extracellular K+ had only negligible effects, but the responses were fully restored in the presence of normal concentrations of extracellular Ca2+. In contrast to TRH, VIP had no demonstrable effect on the Ca2+-dependent action potentials of the GH4 cells.

Animals↗
PubMed1983

Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells).

A thyroliberin (TRH)-responsive particulate bound adenylyl cyclase is present in two rat anterior pituitary tumor cell strains (GH4C1 and GH3) which synthesize and secrete prolactin. At a given Mg2+ concentration, ATP and the guanyl nucleotides GTP and guanyl 5'-yl-imidodiphosphate (GMP-P(NH)P) caused a dose-dependent increase in adenylyl cyclase activity. The maximum response to thyroliberin occurred with ATP and GTP at concentrations above 0.30 mM and 2 microM, respectively. The maximal stimulatory effect of thyroliberin on adenylyl cyclase activity was 2-fold in the presence of GTP. GMP-P(NH)P increased the basal enzyme activity 4- to 10-fold over and above that of equimolar concentrations of GTP but supported poorly the TRH-induced response. Mg2+ caused a dose-dependent increase in the basal enzyme activity and reduced TRH and fluoride-induced responses. Also, Mn2+ and Co2+ stimulated the basal adenylyl cyclase activity while Zn2+, Ca2+, and Cu2+ inhibited the enzyme, and neither cations supported the TRH response. Half-maximal stimulation of the adenylyl cyclase by TRH and half-maximum binding of [3H]TRH to membranes at 35 degrees C were 102 and 56 nM, respectively. Pretreatment with TRH decreased the apparent Vmax of the enzyme and the maximal binding of [3H]TRH. Of 6 TRH analogs tested, only one was able to displace [3H]TRH from its receptor and to increase the adenylyl cyclase activity. We suggest that adenylyl cyclase activation is an early event in the stimulus secretion coupling between TRH and prolactin-producing GH cells.

Adenylyl Cyclases↗
PubMed1983

Inhalation of enflurane and halothane at subanesthetic concentrations and effects on circulating serum testosterone, luteinizing hormone and follicle-stimulating hormone in the male rat.

The present study was carried out in order to investigate the effects of inhaled volatile anesthetic gases in subanesthetic concentrations on circulating hormones essential for normal male reproduction. Male mature rats were exposed daily, up to 11 days, to halothane or enflurane in concentrations up to 500 and 1000 ppm, respectively, and thereafter examined for changes in the serum concentration of circulating testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). No significant changes were found for any of the investigated hormones. Based on our results and other reports it is suggested that short-term repeated exposure to halothane and enflurane at subanesthetic concentrations is not associated with any appreciable acute toxicity on male reproductive functions.

Animals↗
PubMed1983

TSH unresponsiveness, a case report.

A patient with congenital primary hypothyroidism is presented. His thyroid gland had a normal uptake of radioiodine which was independent of endogenous or exogenous TSH, sympathetic B-receptor blockade or prostaglandin inhibition. Infusion of dibuturyl-cyclic AMP increased the uptake of radioiodine and stimulated release of protein bound 131I. He had no goitre even when he did not receive thyroxine, but thyroid histology showed evidence of active epithelium in the presence of adequate substitution with thyroxine. We assume that some unknown factor other than TSH stimulates part of the glandular function in this patient, without leading to adequate formation and release of thyroid hormone.

Aged↗
PubMed1983

Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH.

Forty mg TRH/day given orally for 3 weeks to 8 patients with mild primary hypothyroidism decreased serum TSH from a mean of 4.0 ng/ml +/- 1.2 (SE) to 2.0 ng/ml +/- 0.4 (49%), and their mean incremental TSH response to iv TRH was equally reduced from 8.6 ng/ml +/- 2.5 to 4.0 ng/ml +/- 1.9 (46%). In the same patients serum Prl was 8.2 ng/ml +/- 2.2 before oral TRH treatment and 6.6 ng/ml +/- 1.5 (81%) after treatment, and the mean incremental Prl response to iv TRH was reduced from 43.5 ng/ml +/- 5.0 to 35.9 ng/ml +/- 7.5 (83%). The oral administration of 10 mg of the dopamine antagonist metoclopramide increased mean serum TSH from 0.6 ng/ml +/- 0.1 (SE) to 0.7 ng/ml +/- 0.1 (120%) in euthyroid subjects and from 4.0 ng/ml +/- 1.2 to 5.7 ng/ml +/- 1.6 (145%) in patients with primary hypothyroidism, and mean serum Prl from 8.6 ng/ml +/- 0.8 to 109.5 ng/ml +/- 24.3 (1251%) and from 8.2 ng/ml +/- 2.2 to 119.6 ng/ml +/- 45.5 (1460%), respectively. The incremental TSH responses to iv TRH increased 2.3-fold in euthyroid subjects pre-treated with metoclopramide, while no change was observed in the TSH responsiveness in patients with primary hypothyroidism following metoclopramide pre-treatment. In the euthyroid subjects metoclopramide treatment had no effect on the Prl response to iv TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1982

Trifluoperazine blocks calcium-dependent action potentials and inhibits hormone release from rat pituitary tumour cells.

The effects of trifluoperazine (TFP) on basal and stimulated release of prolactin (PRL) and growth hormone (GH) and on the electrical properties of the membrane were studied in clonal rat pituitary tumour cells in culture (GH3 cells). The basal GH release was inhibited maximally 50% by TFP (13-30 microM) and the K+- and thyroliberin (TRH)-induced stimulation of both PRL and GH release was blocked significantly. The sustained depolarization caused by elevated extracellular K+ concentration and the biphasic membrane potential response to TRH (normally leading to spontaneous action potentials) were not affected by TFP. However, TFP inhibited the Ca2+-dependent action potentials, probably by blocking the voltage sensitive Ca2+ channels in the membrane. We therefore suggest that TFP inhibits hormone release by blocking the uptake of extracellular Ca2+. This action of TFP is probably due to direct membrane effects which are independent of calmodulin.

Action Potentials↗
PubMed1982

Synthesis and androgen effects of 7 alpha,17 beta-dihydroxy-5 alpha-androstan-3-one, 5 alpha-androstan-3 alpha,7 alpha,17 beta-triol and 5 alpha-androstane-3 beta,7 alpha,17 beta-triol.

The steroids 7 alpha,17 beta-dihydroxy-5 alpha-androstan-3-one (7 alpha-hydroxy-Dht), 5 alpha-androstan-3 alpha,7 alpha,17 beta-triol (7 alpha-hydroxy-3 alpha-A'DIOL) and 5 alpha-androstane-3 beta,7 alpha,17 beta-triol (7 alpha-hydroxy-3 beta-A'DIOL) have been synthetized from 7 alpha,17 beta-dihydroxy-4-androsten-3-one (7 alpha-hydroxy-testosterone). The effect of administering 7 alpha-hydroxy-Dht, 7 alpha-hydroxy-3 alpha-A'DIOL or 7 alpha-hydroxy-3 beta-A'DIOL on serum levels of LH, FSH and on ventral prostate and seminal vesicle weight were investigated in gonadectomized adult male rats. Each steroid was administered for seven days in a dose of 300 micrograms per day. No suppression of serum LH or FSH levels was recorded following injections of these 7 alpha-hydroxylated steroids to castrated rats, compared to castrated control rats receiving vehicle only. Administration of 7 alpha-hydroxy-Dht or 7 alpha-hydroxy-3 alpha-A'DIOL to castrated mature rats could maintain ventral prostate and seminal vesicle weights above that of castrated control rats. Administration of 7 alpha-hydroxy-3 beta-A'DIOL to castrated mature rats resulted in ventral prostate weights slightly above castrate control levels, while seminal vesicle weight in such rats were in the same range as castrated control rats. Intraperitoneal administration of testosterone or of 5 alpha-androstane-3 beta,17 beta-diol (3 beta-A'DIOL) to castrated rats maintained activity of the androgen dependent isoenzyme of acid phosphatase in the ventral prostate; 7 alpha-hydroxy-testosterone or 7 alpha-hydroxy-3 beta-A'DIOL showed, however, no effect on this enzymic activity.

Androstane-3,17-diol↗
PubMed1982

Relationship between stimulated prolactin release from GH cells and cyclic AMP degradation and formation.

We have studied the relationship between the prolaction (PRL) release induced by thyroliberin (TRH) and theophylline and the formation and inactivation of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) in cultured rat-pituitary cells (GH3 cells). TRH, which stimulated prolactin release, increased cyclic AMP formation and stimulated transiently both the low- and high-Km cyclic phosphodiesterases. The maximal effect on the phosphodiesterase was observed at 30 mM TRH. The stimulatory effect of TRH on the activity of the cyclic AMP phosphodiesterases was duplicated by incubation of the cells with cyclic AMP (2-10 mM). In washed particulate GH3 cell fractions, TRH increased the adenylyl cyclase activity up to 180%. Treatment of GH3 cells with theophylline stimulated the release of PRL and inhibited cyclic AMP degradation probably leading to the measured increase in cellular concentrations of the nucleotide. The effects of TRH and theophylline on cellular cyclic AMP concentrations and on PRL release were additive. There was a positive correlation between PRL release and cellular cyclic AMP concentration (r = 0.97). The elevations observed in cellular cyclic AMP concentration after TRH treatment are due to increased formation which in turn leads to phosphodiesterase activation. Therefore, cyclic AMP formation appears to be an intermediary step in the stimulus-secretion coupling caused by the tripeptide.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Progestin receptors in prolactin and growth hormone producing tumours in rats.

Progesterone and corticosterone have a similar effect on the production of growth hormone (GH) and prolactin (Prl) by pituitary tumour cells (GH3 cells) in culture. Previously we have shown that progesterone has a high affinity for the glucocorticoid receptors in these cells. Progesterone may therefore exert its effects through binding to the glucocorticoid receptor. The aim of the present study was to investigate if the GH3 tumour cells and an oestrogen induced pituitary tumours, which also produce GH and Prl, possess specific receptors for progesterone. Both the GH3 tumours and the oestrogen induced pituitary tumour were in fact found to possess cytoplasmatic receptor molecules for progesterone by using the potent progestin R5020 as a marker. Isoelectric focusing revealed one binding component (pH 5.9), which was of protein nature. The binding was of high affinity (KD 2 X 10(-9) mol/l). In the oestrogen induced tumour, the maximal binding was 70 fmol/mg cytosol protein. In female rats with GH3 tumours the binding was 55 fmol/mg cytosol protein. Priming of the animals with 1 mg oestradiol-valerate increased the binding to 116 fmol/mg cytosol protein, whereas very little binding was found in GH3 tumours from rats castrated 7 days before sacrifice. The receptors in the oestrogen induced pituitary tumour and the GH3 tumours exhibited high affinity for R5020 and progesterone, whereas corticosterone had no significant affinity for the receptors. Using exchange assay, it was demonstrated that the cytoplasmic progestin receptors could be translocated to the nucleus after administration of progesterone to the animals. Thus, the presence of specific progesterone receptors, different from the glucocorticoid receptors, strongly indicates that athe effects of progesterone on GH and Prl production are mediated through the progesterone receptors.

Animals↗