Summary. During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in a second OGTT. -Human PRL or CB 154 had no significant influence on insulin release due to glucose in the perfused rat pancreas. -These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours.Key words: Prolactin, insulin release, glucose tolerance, pituitary tumours, pancreas perfusions, bromocriptine.Acute administration of ovine prolactin (PRL) has been shown to influence glucose metabolism in animals [1,2], to impair glucose tolerance in hypopituitary dwarfs and in hypophysectomized juvenile-type diabetics [3], and to stimulate lipid metabolism [4]. In order to study the long term effects of endogenous PRL on glucose tolerance and glucose-induced insulin secretion, patients with hyperprolactinaemia were investigated. In vitro experiments with the isolated perfused rat pancreas were undertaken to elucidate the direct effect of hPRL on insulin release. * Presented in part at the 11 th Annual Meeting of the European Association for the Study of Diabetes (EASD), Munich, September 4-6, 1975, and published in abstract form in Diabetologia 11, 357 (1975) Material aud Methods a. In vivo-StudyFifteen female and 11 male patients with hyperprolactinaemia were studied (Tab. 1). Twenty-four patients had a pituitary tumour, one had a craniopharyngioma and one had anormal sella turcica. A galactorrhoeaamenorrhoea syndrome was observed in 9 women.The average body weight was 13 ± 4 % above the ideal body weight and the average age was 34 ± 2 years (mean ± SEM). None of the patients had elevated plasma growth hormone concentrations. Eighteen patients had blunted hGH-secretion after insulin-induced hypoglycaemia. In six subjects TSH levels before and after TRH stimulation were below the lower limit of detection; six patients showed TSH values which were subnormal and two suffered from primary hypothyroidism. Thirteen had secondary hypogonadism, eleven had a latent or manifest secondary adrenal insufficiency and three had diabetes insipidus. The mean basal PRL level (x ± SEM) measured by radioimmunoassay [5] was 2422 ± 800 ng/ml ranging from 47 to 18 860 ng/ml. Our normal range for men is 8.5 to 25 ng/ml and for women up to 37.5 ng/ml. Fourteen patients were on appropriate hormone replacement therapy at the time of the study. Hypothyroidism was treated in all cases except two (Tab. 1) in order to avoid effects of low thyroid hormone levels on glucose tolerance.Fifteen patients (nine females and six males) were treated with bromocripti...
In order to maximize their fitness, organisms in seasonal environments rely on external cues to optimally time their life‐history stages. One of the most important zeitgeber to time reproduction is the photoperiod, but further environmental cues are assessed to fine‐tune reproduction due to year‐to‐year variation in environmental conditions. However, in urbanized environments, the pervasive artificial light at night has altered the natural signal of light and darkness. Accordingly, artificial light at night was repeatedly shown to affect avian reproductive physiology and to advance seasonal reproduction in birds. However, these experiments were mainly conducted in the absence of further environmental cues to facilitate the investigation of the mechanisms which are still poorly understood. Here, we investigate whether the endocrine system of free‐ranging European blackbirds (Turdus merula) correlates with the amount of artificial light at night along a rural to urban gradient while the birds still encounter complementary environmental cues including seasonal variation in day length and temperature. Testosterone and estrone were assessed as metabolites in fecal samples and corticosterone in blood from mist‐netted blackbirds. We demonstrate that seasonal fluctuations in abiotic factors, individual conditions, but also light at night affect the reproductive and stress physiology of wild European blackbirds. Elevated artificial night light intensities were significantly positively correlated with corticosterone and negatively with female estrone levels. No effects of artificial light were found for testosterone levels. Our results suggest that female blackbirds in particular perceive even low levels of artificial light at night as a weak but chronic stressor that interacts with the hypothalamic‐pituitary‐gonadal axis and leads to a reduced secretion of reproductive hormones. These findings point out that the impacts of light pollution are diverse and we only slowly disentangle its multiple effects on physiology, ecology, and biodiversity.
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vivo imaging, micro-computer tomography, and immunostainings verified that an ATF2KO/TROP2high status triggered tumor invasiveness in in vivo mouse and chicken xenograft models. In silico analysis provided direct support that ATF2low/TROP2high expression status defined high-risk CRC patients. Finally, our data demonstrate that ATF2 acts as a tumor suppressor by inhibiting the cancer driver TROP2. Therapeutic TROP2 targeting might prevent particularly the first steps in metastasis, i.e., the de-adhesion and invasion of colon cancer cells.
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