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- Ekström, Peter, et al.
(författare)
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Localization of 2-[125I]lodomelatonin binding sites in the brain of the atlantic salmon, salmo salar L.
- 1992
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 55:5, s. 529-537
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Tidskriftsartikel (refereegranskat)abstract
- The photosensory pineal organ of teleost fish shows a circadian rhythm in melatonin synthesis, and melatonin is known to influence a number of physiological functions. However, the target sites for melatonin are not known. We have investigated the distribution of melatonin binding sites in the brain of the salmon, Salmo salar. Brains were collected for receptor binding assay and autoradiography at each of three time points; just after lights on, just before lights off, and in the dark at midnight (photoperiod light-dark 12: 12, lights on at 08.00 h, lights off at 20.00 h). Specific binding of 2-[125I]iodomelatonin was observed in several brain areas. High densities were associated with (1) the optic tectum, (2) the preoptic area, (3) an area encompassing the magnocellu-lar superficial pretectal nucleus ('nucleus rotundus') and the glomerular complex, (4) the inferior lobes of the hypothalamus, (5) the lateral mesencephalic tegmentum including the torus semicircularis, and (6) the molecular layer of the cerebellum. No binding was observed in the pineal organ or in the pituitary. We observed no differences in labeling between brains collected at different time points, except in the preoptic area where binding was high at 20.00 and 24.00 h, but low at 08.00 h, and in the corpus cerebelli, where labeling in the molecular laver was higher at 24.00 and 08.00 h than at 20.00 h. Saturation experiments with crude brain membranes indicated the presence of a single binding site with no significant differences related to the time of day, with Kd values ranging from 30 to 54 pM, and Bmax values from 7.0 to 10.8 fmol/mg protein. Nonspecific binding, determined with 0.1 μM melatonin, was < 20%. The Kd and Bmax, values are in the same range as those reported for the so-called high-affinity binding site in mammalian neural tissue.
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| 2. |
- Sundlöv, Anna, et al.
(författare)
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Pituitary function after high-dose 177Lu-DOTATATE therapy and long-term follow-up.
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:4, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- The pituitary gland has a high expression of somatostatin receptors (SSTRs) and is therefore a potential organ at risk for radiation-induced toxicity after 177Lu-DOTATATE treatment.To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based 177Lu-DOTATATE to detect possible late toxicity.68 patients from a phase II clinical trial of dosimetry-based, individualized 177Lu-DOTATATE-therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF1-axis, gonadotropins, adrenal and thyroid axes were analyzed from baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using boxplots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed vs % change in IGF1-levels over time.A statistically significant decrease in the levels of IGF1 was found (p<0.005), which was correlated to the number of treatment cycles (p=0.008) and absorbed radiation dose (p=0.03). A similar decrease, although non-significant, was seen in the gonadotropins in post-menopausal women, while in men there was an increase during the first years post-therapy, after which the levels returned to baseline. No change was observed in the adrenal nor thyroid axes.No signs of severe endocrine disorder were detected, although a significant decrease in the GH/IGF1-axis was found, where dosimetric analyses indicate radiation-induced damage to the pituitary gland as a probable cause.
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