Biomedical subjects

T Bjøro

Publications and source records attributed to T Bjøro.

At least 37 records · Page 2Linked to original sources

PubMed1993

Long-term treatment of macroprolactinomas with CV 205-502.

The long-term efficacy and tolerability of CV 205-502, a non-ergot dopamine agonist with D-2 receptor affinity, were studied for up to 36 months in 16 patients with macroprolactinomas. Prolactin values were reduced in all cases, becoming either normalized or suppressed in 12. The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects. Concomitantly we observed improvement in gonadal function, galactorrhea, headache, libido and general well-being. Adverse reactions were experienced by 15 patients during dosage increment and caused one patient to discontinue the medication. Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205-502, sufficient to normalize PRL levels in three. Two patients experienced serious adverse events, causing the discontinuation of treatment in one case. In eight patients treatment with CV 205-502 and bromocriptine could be compared. Three patients responded better to CV 205-502 than to bromocriptine treatment. Only one patient preferred bromocriptine to CV 205-502 for long-term treatment. We conclude that CV 205-502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas. CV 205-502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed.

Adult↗

PubMed1993

Different responses in little and bigbig prolactin to metoclopramide in subjects with hyperprolactinemia due to 150-170 kD (bigbig) prolactin.

We have studied in vivo induction of serum prolactin (PRL) levels in four females and one male, and regulation of PRL in the menstrual cycle in three females all with hyperprolactinemia with large amounts (72-92%) of bigbig PRL (MW 150-170 kD). Metoclopramide (MTC) iv induced a 4-29-fold increase in little PRL (25 kD PRL) at 30 min, while the increase in 150-170 kD PRL was 1.1-2.2-fold. The maximal response in 150-170 kD PRL was seen after 2-6 h, and the decrease after the maximal PRL values for 150-170 kD PRL was delayed compared to the decrease in 25 kD PRL. The different kinetics for 25 kD PRL and 150-170 kD PRL was responsible for the prolonged increase in total PRL seen in the subjects with large amounts of 150-170 kD PRL compared to the controls. The percentage of 150-170 kD PRL decreased to 29-60% at 30 min and returned to unstimulated values after 6-24 h. In contrast, prolonged stimulation of PRL secretion, as in the luteal phase, did not change the percentage of 150-170 kD PRL. In a male subject secreting large amounts of 150-170 kD PRL the increase in PRL after MTC was less, while the temporal changes in the 25 kD PRL levels were almost the same as in the females.

Adult↗

PubMed1993

Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium.

Epidermal growth factor (EGF) stimulated the prolactin (PRL) synthesis and release from the GH4C1 cells in a dose-dependent manner. The ED50 was between 10(-11) and 10(-10) mol/l. The maximal effect was obtained at 10(-9) mol/l EGF for the release, and 10(-8) mol/l EGF for the synthesis. EGF stimulated the release of PRL from cell perfusion columns after a lag period of about 30 s. The maximal secretion of PRL occurred about 60 s after the start of stimulation. The PRL secretion declined to basal levels within 2 min. The EGF-stimulated PRL release was additive to the secretion evoked by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). An instantaneous increase in the intracellular concentration of free calcium, [Ca2+]i, of the GH4C1 cells was observed after the administration of EGF. EGF modified neither the basal nor the TRH-stimulated inositoltrisphosphate production in the GH4C1 cells, and EGF did not show any effect on the cyclic adenosine monophosphate production of these cells.

Animals↗

PubMed1993

Inhibitors of the arachidonic acid metabolism attenuate the thyroliberin (TRH) stimulated prolactin production without modifying the production of inositolphosphates in GH4C1 pituitary cells.

Some arachidonic acid metabolites might be among the intracellular signalling substances that regulate hormone release. We report that the phospholipase A2 and diacylglycerol lipase inhibitor quinacrine (1-10 mumol l-1) inhibited the thyroliberin stimulated prolactin (rPRL) production in a dose-dependent way in a rat pituitary tumour cell line (GH4Cl cells). The lipoxygenase inhibitor nafazatrom (5-50 mumol-1) also dose-dependently inhibited the thyroliberin stimulated rPRL production, while the cyclo-oxygenase inhibitor indomethacin had no such effect on rPRL production. The inhibitors of the arachidonic acid metabolism (quinacrine, ETYA and nafazatrom) had no effect on the accumulation of inositolpolyphosphates indicating that the arachidonic acid metabolites are not involved in the regulation of the phospholipase C activity.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1992

Long-term glycemic control and kidney function in insulin-dependent diabetes mellitus.

In this paper we examined the relationship between blood glucose control and initiation and progression of increased urinary albumin excretion. In this seven year Oslo study 45 insulin-dependent diabetes mellitus patients were initially randomized into three different modes of treatment: continuous subcutaneous insulin infusion (CSII), multiple injections, or two injections a day. After four years, the patients were free to choose their treatment, and therefore the data were analyzed according to mean HbA1 during seven years. The mean HbA1 was 11.2% (2.2) (SD) at start, and 9.5% (1.5) at seven years, which was a significant long-term improvement (P less than 0.001). Eight out of 10 patients with mean seven year HbA1 less than 8.5% improved their albumin excretion rate, and patients with mean HbA1 greater than 10% had an increased albumin excretion rate (from 26 mg/24 hr to 91 mg/24 hr, P less than 0.02). The glomerular filtration rate decreased slightly regardless of mean HbA1 level. Systolic blood pressure increased significantly regardless of mean HbA1. Diastolic blood pressure was unchanged in the patients with mean HbA1 less than 10%, but increased slightly (NS) in patients with HbA1 greater than 10%. We conclude that mean blood glucose as measured by glycosylated hemoglobin is a main determinant in the progression of urinary albumin excretion in insulin dependent diabetics, and near normoglycemia improves urinary albumin excretion.

Adolescent↗

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↗

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

Effect of Diamphidia toxin, a Bushman arrow poison, on ionic permeability in nucleated cells.

The effect of Diamphidia toxin, isolated from pupae of Diamphidia nigro-ornata, was tested on two different cell lines (GH4C1 cells and HL-60 cells) and on human lymphocytes. The toxin raised intracellular Ca2+ concentration, as assessed with quin 2, in a dose-related manner in all three cell types. The effect was abolished when extracellular Ca2+ was chelated by EGTA. Low concentrations of the toxin evoked a delayed as well as a smaller response. The response time was also temperature-dependent, with a Q10 of about 2. Low, but effective concentrations of the toxin did not affect cell membrane integrity, as tested with Trypan blue, and induced a seemingly physiological release of prolactin from the GH4C1 cells. Diamphidia toxin's effect on the membrane permeability of GH4C1 cells was further investigated with patch-clamp techniques. The toxin appeared to increase the conductance for all small ions without affecting the normal ionic channels present in these cells. We conclude that Diamphidia toxin has a general effect on the plasma membrane of different cell types and thereby increases, probably non-specifically, the permeability for small ions.

Ammonium Sulfate↗

PubMed1990

Ovarian stimulation in previous failures from in-vitro fertilization: distinction of two groups of poor responders.

Forty-three patients who responded poorly to previous stimulation with clomiphene citrate (CC)/human menopausal gonadotrophin (HMG) for IVF were followed during 70 further cycles. Eighteen patients had a normal FSH response to CC in the previous cycle, while 25 had an abnormal FSH response. Three stimulation protocols were used: buserelin/HMG, CC/HMG and HMG only. No difference between the two groups was observed in the dose of HMG used for any stimulation protocol. More cycles were cancelled due to a poor response in the abnormal response group compared to the normal response group. In the completed cycles, the maximum oestradiol level and number of oocytes retrieved were lower in the abnormal response group compared to the normal response group. The total pregnancy rate per patient, including spontaneous conceptions during the study period, was lower in the abnormal response group compared to the normal response group, 4 versus 33%. We conclude that poor responders with an abnormal FSH response to CC have a latent ovarian failure with a low chance of success in further IVF attempts.

Adult↗

PubMed1989

[Thyroid dysfunction and thyroid antibodies in a population group over the age of 70. A prevalence study from Oslo and Naeröy].

The prevalence of thyroid dysfunction and thyroid antibodies was investigated in a small rural community (Naerøy) and in Oslo. Attendance rates in Naerøy and Oslo were 99 and 71%, respectively. The prevalence of undiagnosed latent hypothyroidism and primary hypothyroidism was 4.0 and 5.3% in women in Oslo and Naerøy respectively and 0 and 3.5% in men. Undiagnosed hyperthyroidism was detected in 1.2% of men in Naerøy and in 1% of women in Oslo. Antibody to the thyroid microsomal antigen in titre greater than or equal to 400 was detected in 10.2 and 17.5% of women and 7.3 and 7.2% of men in Oslo and Naerøy, respectively. Among women with antibody to the thyroid microsomal antigen in both Oslo and Naerøy, and among men in Naerøy, the prevalence of past or present thyroid dysfunction was increased.

Age Factors↗

PubMed1989

Vasoactive intestinal peptide (VIP) may reduce the removal rate of cytosolic Ca2+ after transient elevations in clonal rat lactotrophs.

The prolactin-producing rat anterior pituitary GH4C1 cells possess Ca2+-activated K channels which are activated by physiological elevations of the cytosolic Ca2+ concentration even at membrane potentials more negative than the normal level of about -50 mV. Whole-cell current recordings showed a marked outward tail current following depolarizing voltage steps to 0 mV from a holding potential close to the normal membrane potential. The half-time of this tail current was about 1.3 s after a 4-s depolarization step. The GH4C1 cells also possess voltage-activated Ca channels, and we conclude that this tail current is a Ca2+-activated K+ current for the following reasons: (1) The reversal potential for the tail current was close to the K+ equilibrium potential for a range of transmembrane K+ gradients. (2) The tail current was blocked by a Ca2+ antagonist, and the voltage dependence of this current closely mirrored the voltage dependence of the isolated Ca2+ current. The time-course of the decline of the tail current thus reflects the removal rate of the Ca2+ entering the cytosol through voltage-dependent Ca channels during the depolarizing voltage step. VIP stimulates prolactin secretion from GH4C1 cells, and this peptide prolonged the half-time of the tail current by about 47% in 63% of the cells. This indicates that VIP may prolong the transient cytosolic Ca2+ elevations following the action potentials in these cells. Such a mechanism might be an important factor for the control of the cytosolic Ca2+ level, and hence hormone secretion.

Animals↗

PubMed1988

Phorbol esters and thyroliberin have distinct actions regarding stimulation of prolactin secretion and activation of adenylate cyclase in rat pituitary tumour cells (GH4C1 cells).

The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhances the effects of TRH on phase II of prolactin secretion as well as on hormone synthesis at both low and high TPA receptor occupancy. Furthermore TPA, but not the biologically inactive substance 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), stimulates the particulate bound adenylate cyclase with a time course paralleling that of TRH activation. However, the combined additions of TRH and TPA activate this cyclase in an additive manner while the Gpp(NH)p- and the forskolin-sensitive enzyme are unaffected by TPA addition. Polymyxin B, which inhibits protein kinase C, abolishes activation of adenylate cyclase by TPA without interfering with the stimulatory action of TRH. Also, when phosphatase activity is preferentially inhibited by pretreatment of the cells with sodium vanadate, the TRH-sensitive cyclase is unaltered, while TPA activation is obliterated. Maximal stimulation of adenylate cyclase by cholera toxin pretreatment, obliterated the actions of TRH and TPA. Cells pretreated with pertussis toxin retained their TRH-sensitive cyclase, however, TPA-responsiveness was lost. We therefore suggest that the action of TPA as it relates to activation of adenylate cyclase, is probably mediated via the Gi component of the adenylate cyclase complex, while TRH stimulates the enzyme via the classical pathway involving the stimulatory GTP binding protein (Gs).

Adenylyl Cyclases↗

PubMed1988

Thyrotropin-releasing hormone-stimulated inositol trisphosphate formation is liable to thyrotropin-releasing hormone-induced desensitization by a calcium-dependent mechanism.

In cultured rat pituitary cells (GH4C1 cells) the ability of thyrotropin-releasing hormone (TRH) to stimulate phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phospholipase C-type reaction was confirmed. The dose-response relationship for the TRH-stimulated phospholipase C was elucidated as was the relationship between the various inositol phosphates formed during the first few seconds after stimulation. The TRH-stimulated phospholipase C was subject to desensitization by repeated TRH treatment of cell cultures. This desensitization was dependent on the dose of TRH during preincubation. Following desensitization no decline in the levels of PIP2 was detected, even in the presence of decreased levels of PIP2 precursors. The TRH-stimulated phospholipase C activity was not attenuated following pretreatment with 12-O-tetradecanoylphorbol 3-acetate (TPA) to stimulate protein kinase C activity, and TRH also induced desensitization in the presence of the protein kinase C inhibitor polymyxin B. Thus, regulation of protein kinase C activity seemed not to be involved in the desensitization process. It is suggested that the ability of TRH to desensitize its own receptors and their link to phospholipase C, is mediated by the rise in intracellular calcium that is initiated by the TRH-receptor interaction.

Animals↗

PubMed1988

Somatostatin inhibits prolactin secretion by multiple mechanisms involving a site of action distal to increased cyclic adenosine 3',5'-monophosphate and elevated cytosolic Ca2+ in rat lactotrophs.

The release of prolactin (PRL) from a clonal cell-line of anterior pituitary cells (GH4C1) was inhibited by somatostatin (SRIH) in a dose-dependent manner (ED50 nM). The inhibition (20% of control levels) was detectable within 50 s and maximal within 90 s. Thyroliberin (TRH) enhancement of PRL secretion was biphasic. SRIH inhibited both phases equally. Ionomycin in combination with the phorbol ester, TPA, mimics the TRH-elicited PRL release, and SRIH partly inhibited this effect. SRIH had no effect on TRH-stimulated formation of inositol trisphosphate, and only small effects on TRH-activated adenylate cyclase. Vasoactive intestinal peptide (VIP) and forskolin stimulated cAMP formation and PRL release potently. SRIH inhibited both effects of VIP and forskolin, and there was a close correlation between the inhibition of PRL secretion and cAMP accumulation. 8-Bromo-cAMP enhanced PRL release, an effect that was also partly reduced by SRIH. The Ca2+ channel activator, BAY-K-8644 and high extracellular K+ increased PRL release, and SRIH caused a partial reduction in the release response to both secretagogues. SRIH lowered [Ca2+]i, and markedly reduced the rise in [Ca2+]i elicited by TRH, VIP and K+. SRIH did not influence the Ca2+ spikes recorded in Na+-free solution, and had no effect on the TRH-induced membrane potential changes. Our results demonstrate that SRIH may inhibit PRL release from GH4C1 cells by (1) inhibiting hormone-sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]i. None of these effects is, however, sufficient to explain all the effects of SRIH, suggesting that SRIH also exerts a major action at a step subsequent to cAMP accumulation and [Ca2+]i elevation. Since the GH4C1 cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems.

Animals↗

PubMed1988

Prevalence of thyroid dysfunction in elderly subjects. A randomized study in a Norwegian rural community (Naerøy).

The prevalence of thyroid dysfunction was investigated in a small, rural community located at the coast in Middle Norway. Two hundred persons (114 women and 86 men) of the total 802 persons over 70 years of age in the community were examined regarding thyroid dysfunction. Blood samples were drawn from 197 (113 women and 84 men). In women previously diagnosed hypothyroidism was found in 3.5% and previously diagnosed hyperthyroidism in 0.9%. In men no previously diagnosed thyroid disease was found. Undiagnosed primary hypothyroidism (TT4 less than 70 nmol/l and TSH greater than 6 mU/l) was found in 1.8% and 1.2% of women and men, respectively. Latent hypothyroidism (TT4 70-150 nmol/l and TSH greater than 6 mU/l) was found in 3.5% and 2.4%, and borderline hypothyroidism (TSH 4.5-6.0 mU/l) in 3.5% and 2.4%, respectively. Undiagnosed hyperthyroidism was not found in women but in 1.2% of men. Antibody to the thyroid microsomal antigen (TMA) greater than or equal to 400 was detected in 17.5% of women and 9.6% of men. Clearly elevated serum thyrotropin (TSH) concentrations or previously diagnosed thyroid disease were found in 21.7% and 37.5% of the TMA positive women and men, respectively.

Age Factors↗

PubMed1988

Reduction of urinary albumin excretion after 4 years of continuous subcutaneous insulin infusion in insulin-dependent diabetes mellitus. The Oslo Study.

Urinary albumin was studied in 45 patients with insulin-dependent diabetes in a 4-year prospective randomized trial, comparing continuous sc insulin infusion (CSII), multiple insulin injections, and conventional treatment with twice daily injections. Strict blood glucose control was obtained with CSII and multiple injections, better than with conventional treatment (2P less than 0.01): mean glycosylated haemoglobin (% HbA1 +/- SEM) after 4 years: CSII 9.0 +/- 0.4%; multiple injections 9.4 +/- 0.4%; conventional treatment 10.5 +/- 0.5. A total of 696 24-h urine specimens were collected. After 4 years of CSII from the time of randomization, urinary albumin excretion was reduced (26 +/- 5 to 16 +/- 4 mg/24 h, mean +/- SEM, 2P less than 0.01), when compared with conventional treatment (2P = 0.01), when compared with conventional treatment (2P = 0.01) where no change was observed (21 +/- 4 to 22 +/- 6 mg/24 h, n.s.). The reduction observed during multiple injection treatment was not significant (17 +/- 3 to 14 +/- 3 mg/24 h). Long-term near-normoglycaemia may influence the mechanisms leading to albuminuria in diabetes, if introduced at an early stage of the disease.

Adolescent↗

PubMed1987

Cyclic AMP-mediated suppression of normal and neoplastic B cell proliferation is associated with regulation of myc and Ha-ras protooncogenes.

Cyclic AMP functions as a negative regulator of cell proliferation in a variety of cell systems. We show here that the proliferation of normal and neoplastic B cells can be inhibited by high intracellular levels of cAMP. Thus forskolin treatment of the neoplastic B precursor cell line Reh induced a rapid increase in the cAMP level, which was followed by an accumulation of cells in the G0/G1 phase of the cell cycle over a period of 2-3 days. Similar inhibition of Reh cell proliferation after 3 days was observed whether forskolin was present continuously or only during the first 5 hr. Both c-myc and c-Ha-ras protein levels were transiently down-regulated at 4 hr of forskolin treatment, suggesting that these protooncogenes play a role in the process leading to cAMP-mediated growth cessation. Northern-blot analysis showed that the steady-state levels of c-myc RNA rapidly declined in all phases of the cell cycle, to return to control levels within a time period of 24 hr. In contrast, the c-Ha-ras mRNA level was steadily maintained. Thus the expression of c-myc and c-Ha-ras protein was regulated at different metabolic levels. The reduced proliferative capacity of the B precursor cell line in the presence of forskolin was not linked to induced differentiation. This was judged from the lack of appearance of three different B cell differentiation markers; cytoplasmic immunoglobulin heavy chain and two antigens recognized by the monoclonal antibodies B1 (CD20) and HH1 (CD37). We also showed that forskolin partially inhibited the proliferation of normal B lymphocytes stimulated by anti-immunoglobulins (anti-mu) and B cell growth factor (BCGF). The burst of c-myc mRNA during activation of normal B cells was also reduced by forskolin.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

A permissive role for extracellular Ca2+ in regulation of prolactin production by 1,25-dihydroxyvitamin D3 in GH3 pituitary cells.

A clonal strain of rat pituitary tumor cells (GH3) that spontaneously synthesizes and secretes prolactin (PRL) and growth hormone (GH) was used as model system to study the mechanism of action of 1,25-(OH)2D3. We have previously demonstrated that these cells possess specific cytosol binding proteins for 1,25-(OH)2D3 (Haug and Gautvik, 1985). When the GH3 cells were incubated in a serum-free, chemically defined medium of low extracellular Ca2+ concentration, 1,25-(OH)2D3 stimulated PRL production in a dose-dependent manner. The stimulation was detectable at 10(-11) M, and the maximum effect (2-fold increase) was observed at 10(-9) M (ED50 = 2 x 10(-11) M). The dose-response curve was bell-shaped, and at 10(-6) M 1,25-(OH)2D3 even suppressed PRL production to about 75% of controls. The stimulatory effect was first seen after 2 days and was maximal after 4 days. On a molar basis 25-OHD3 and 1-OHD3 were at least 100 times less potent than 1,25-(OH)2D3, while 24,25-(OH)2D3 had no effect on PRL production. At an extracellular concentration of Ca2+ as low as 4 x 10(-5) M the stimulatory effect of 1,25-(OH)2D3 was small (1.3-fold). Increasing extracellular Ca2+ to 1.5 x 10(-4) M increased the 1,25-(OH)2D3-induced PRL response to 2.1-fold. In contrast to the biphasic effect of 1,25-(OH)2D3 on PRL production, GH production was decreased to about 60% of controls at 10(-8) M and above. These findings indicate that in serum-free medium the stimulatory effect of 1,25-(OH)2D3 on PRL production is critically dependent on the concentration of extracellular Ca2+.

Animals↗