Truls Brinck-Johnsen

Low levels of dietary methylmercury inhibit growth and gonadal development in juvenile walleye (Stizostedion vitreum)

Mercury levels in the aquatic environment of North America have been increasing, raising the possibility that this highly toxic heavy metal might alter fish populations. Previous investigations have demonstrated toxic effects of mercury on teleost reproduction, but these findings were observed following unrealistically high exposures. In this study, we used concentrations frequently observed in North American lakes to investigate the effects of dietary methylmercury on growth, gonadal development, and plasma cortisol levels in juvenile walleye (Stizostedion vitreum). For a period of 6 months, two groups of walleye were reared on untainted catfish fillets, while two test groups were fed fillets injected with methylmercury, one group receiving 0.1 kg Hg g-’ food (low-mercury diet) and the other receiving 1 .O 1.18 Hg g 1 food (high-mercury diet). After the exposure period, fish fed the low- and high-mercury diets had mean body burdens of 0.254 f. 0.015 pg Hg g-l and 2.37 f 0.09 Fg Hg g-‘, respectively. Dietary mercury significantly impaired both growth and gonadal development in males, which was apparent as reduced fish length, weight, and gonadosomatic index. Testicular atrophy was observed in fish fed the mercury-tainted fillets, but was nonexistent in control animals. Mercury also suppressed plasma cortisol in juveniles (sexes combined). The findings of this study suggest that dietary methylmercury, at levels currently found in the aquatic environment, might reduce juvenile survival by impairing growth and immune function. Furthermore, these results suggest that methylmercury might also affect reproductive potential of teleosts by impairing testicular development in young.

The renin-angiotensin system during pregnancy in chronically instrumented, conscious rats

Whether the renin-angiotensin system is activated during rat gestation is controversial. Therefore we serially assessed plasma renin activity in unrestrained, chronically instrumented conscious rats during pregnancy and the postpartum period. Plasma renin activity was 3.26 +/- 0.30, 2.80 +/- 0.31, and 2.70 +/- 0.26 ng.ml-1.hr-1 on gestational days 6, 12, and 20, respectively. When the same rats were studied after delivery, plasma renin activity was 1.87 +/- 0.29, 1.81 +/- 0.09, and 2.31 +/- 0.35 ng.ml-1.hr-1 on postpartum days 3, 6, and 11, respectively. Levels measured during pregnancy were significantly greater than in the postpartum period (p less than 0.05 or less than 0.01). We then evaluated potential functional consequences of the renin-angiotensin system in gravid rats. Near term, renal hemodynamics fall from the peak levels of midgestation; we tested whether angiotensin II mediates this apparent vasoconstriction. Captopril (1.5 mg/kg, 1.5 mg.kg-1.hr-1) was acutely administered to lower circulating angiotensin II. The drug produced an 80% inhibition of angiotensin I pressor response, a tenfold elevation in plasma renin activity, but caused the same degree of mild renal vasodilation in rats whether they were virgin or pregnant. We also tested whether prior occupancy of receptors by endogenous hormone or receptor downregulation mediates the attenuated pressor response to angiotensin II observed during late pregnancy. Acute administration of captopril failed to augment refractory pressor responsiveness. Chronic treatment with enalaprilat (2.0 mg.kg-1.day-1 by osmotic minipump) also did not restore pressor responsiveness. But, in our hands, chronic administration of enalaprilat most likely failed to lower plasma angiotensin II. In summary, we suggest that during rat gestation (1) the renin-angiotensin system is activated, (2) angiotensin II does not mediate the apparent renal vasoconstriction observed near term, (3) prior receptor occupancy by endogenous hormone is not responsible for the attenuated pressor response to angiotensin II, and (4) long-term treatment with enalaprilat can produce hypotension without reducing plasma concentrations of angiotensin II.

Hypodiploid, pseudodiploid, and normal karyotypes prevail in cytogenetic studies of medullary carcinomas of the thyroid and metastatic tissues

Medullary carcinoma of the thyroid (MCT), often a dominantly inherited neoplasm, derived from intrathyroid C-cells of neural crest origin, is one of the solid tumors least studied cytogenetically. The cells are difficult to grow in culture, only two cell lines having ever been established. Cytogenetic studies of only 5 tumors have been reported previously. In this paper we report on the cytogenetic analyses of 8 specimens of primary and/or metastatic MCT tumor tissue from 6 patients with familial disease, including more recent metastatic tumors in lymph node and femur of a patient whose thyroid and earlier lymph node metastases were described previously. Some of these specimens were harvested sequentially over time. Hypodiploid or diploid modal numbers prevailed with normal, pseudodiploid, or hypodiploid karyotypes.

Estrogen production by an established cell line from pulmonary small cell anaplastic carcinoma

Radioimmunoassays demonstrated the presence of estradiol-17β in growth medium from DMS-44, a continuous cell line obtained from pulmonary small cell anaplastic carcinoma; other steroids such as testosterone and cortisol were not present in measurable amounts. To study further the ability of DMS-44 cells to produce estrogens, [3H]-testosterone or [3H]-androstenedione was incubated with cells for 24 h. [3H]-estrone and [3H]-estradiol-17β were isolated from the incubation medium by extraction. Partition and thin layer chromatography. The two estrogens were identified by chromatography after addition of authentic [14C]-estrone to the fractions presumed to contain [3H]-estrone and authentic [14C]-estradiol-17β to that of [3H]-estradiol. Estradiol-17β was favored over estrone as the main estrogen formed both from testosterone and androstenedione. The estradiol-17β fraction was repeatedly chromatographed in several thin layer Chromatographic systems, reaching constant Tritium: Carbon-14 ratio. These findings, together with the radioimmunoassay data, are considered conclusive evidence for the formation of estradiol-17β by small cell carcinoma cell lines in vitro.

Is cortisol metabolized as it dissociates from glucocorticoid receptors in thymus cells

Abstract To investigate the possibility that metabolic transformations of a steroid hormone are associated with its release from nuclear receptors, rat thymus cells were incubated with [ 3 H]-cortisol at 37°C to form nuclear glucocorticoid-receptor complexes. Then, by means of successive timed dilutions with buffer at 37°C, the receptor-bound radioactivity was isolated after it had been allowed to dissociate from the receptors and leave the intact cells under physiological conditions. Analysis of this radioactivity showed that it consisted of essentially pure [ 3 H]-cortisol. It is therefore concluded that no metabolic transformation is necessary for or accompanies the release of Cortisol from the nuclear glucocorticoid receptors of thymus cells.

Gestational changes in hamster adrenocortical function

Abstract Plasma cortisol levels in the hamster increase approximately 100 fold (from 0.3 to 30 μg/ 100ml) towards the end of gestation. Bilateral adrenalectomy shows that the adrenals are the primary source of cortisol during hamster pregnancy. Using endotoxin injections as a stress stimulus and an activator of the hamster hypothalamo-hypophyseal-adrenocortical system, the pregnant hamster exhibits a capacity to produce unusually large quantities of cortisol; cortisol increases following this stress stimulus to well over 100 μg/ 100ml. Destruction of the fetuses with H-1 virus but leaving the placenta intact, does not adversely affect the adrenal function, but increases the cortisol output, probably due to the stress involved. Corticotropin stimulates, and dexamethasone causes a typical suppression of cortisol secretion in the pregnant hamster. This demonstrates that even during the gestational hyperfunction, the adrenal cortex is still under normal physiological control. If placental factors influence cortisol secretion, the negative feedback system acting by way of the hypothalamus and the pituitary, still appears to be in control.

Inhibitory Effect of Streptozotocin on Tumor Development in Transgenic Mice Bearing an Elastase I-SV40 T-Antigen Fusion Gene

Transgenic mice, bearing a fusion gene of rat elastase I promoter and SV40 T-antigen, developed acinar cell tumors of the pancreas, as predicted by the model. In addition, they developed insulinomas and somatostatin (delta)-cell hyperplasia of the pancreatic islets. The insulinomas and the delta-cell hyperplasia appeared to be functional, as evidenced by changes in plasma glucose, insulin, and somatostatin. Streptozotocin, which has been shown to inhibit pancreatic carcinogenesis in the hamster model, significantly reduced the numbers of insulinomas and delta-cell hyperplasias. Streptozotocin did not cause a statistically significant reduction in exocrine tumors.