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A Lerchl

Publications and source records attributed to A Lerchl.

At least 37 records · Page 2Linked to original sources

Initial expression of the common alpha-chain in hypophyseal pars tuberalis-specific cells in spontaneous recrudescent hamsters.

When exposed to short-day conditions, hamsters and other long-day breeders undergo gonadal regression. With chronic exposure to short days, however, the animals become photorefractory and gonadal recrudescence occurs. The underlying mechanism for this insensitivity is still unknown. There is growing evidence, however, that specific cells of the pituitary pars tuberalis (PT) mediate these photoperiod/nonphotoperiod-dependent changes as a direct or indirect "Zeitgeber" for the endocrine system. We investigated messenger RNA (mRNA)/protein formation for several hypophyseal hormones (beta-TSH, beta-LH, PRL, common alpha-chain) in the pars distalis (PD) and PT of female Djungarian hamsters in long photoperiod (LP) and after 18, 28, and 38 weeks of short photoperiod (SP). As indicated by gonadal and body weight, the hamsters displayed gonadal regression after 18 and 28 weeks of SP; after 38 weeks of SP, all animals showed recrudescence. At 18 and 28 weeks of SP, only PRL mRNA and protein levels were significantly reduced in the PD and returned to LP values after 38 weeks of SP. The expression of hypothalamic tyrosine hydroxylase in the arcuate nucleus that was determined by immunocytochemistry and by in situ hybridization was also down-regulated in SP18 and SP28 with increasing levels at SP38. Urinary 6-sulfatoxymelatonin levels were elevated in SP with highest levels in the SP18 group. In the PT, beta-TSH mRNA and protein were not detectable in all SP groups compared with the moderate signal intensity in LP. The common alpha-chain mRNA and protein, however, which were also reduced in the animals of the SP18 group, were already elevated after 28 weeks of SP and nearly reached LP-levels after 38 weeks of SP. These results show that, in contrast to LH and TSH, PRL expression in the PD is a sensitive indicator for photoperiod dependent changes of the endocrine system and seems to be tyrosine hydroxylase independent. The increase of common alpha-chain expression in PT-specific cells depending upon duration of SP that precedes the hormonal changes in the PD leads us to speculate that PT-specific cells initiate spontaneous recrudescence via a PT-PD pathway.

Animals↗

In vitro fertilizing capacity of sperm from FSH-treated photoinhibited Djungarian hamsters (Phodopus sungorus).

In hypogonadal male Djungarian hamsters FSH alone can induce normal spermatogenesis. However, for the induction of mating behavior, supplementation with testosterone is necessary. We have here investigated, by in vitro fertilization, whether sperm produced by photoinhibited hamsters treated with FSH alone can fertilize without testosterone. Photoinhibited hypogonadal male Djungarian hamsters were injected daily with human FSH (10 IU; Fertinorm) for 5-7 weeks. The hormone stimulated regrowth of the testes. Neither body weight nor the weights of the androgen-dependent organs-epididymides, prostates, accessory glands-showed significant differences from photoinhibited controls; furthermore FSH treatment did not raise intratesticular or serum testosterone levels. In eleven out of the twelve FSH-treated photoinhibited hamsters, elongated spermatids were found in the testes; in five out of nine epididymides, sperm was found by histological examination. In two out of the twelve FSH-treated hamsters, the amount of sperm in the caudal part of the epididymis was sufficient for in vitro fertilization with oocytes collected from superstimulated females. These spermatozoa fertilized 16-29% of the oocytes. Spermatozoa from photostimulated controls produced similar levels of fertilization.

Animals↗

Study on pineal function and DMBA-induced breast cancer formation in rats during exposure to a 100-mG, 50 Hz magnetic field.

Reduction of circulating melatonin levels by pinealectomy or constant light has previously been shown to enhance the development and growth of mammary cancers induced by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Since pineal melatonin production can also be disturbed by electromagnetic field exposure, we studied whether there is an association between melatonin depression by magnetic field (MF) exposure and DMBA-induced breast cancer growth in female rats. In the present experiments, 216 female Sprague-Dawley rats were divided into 4 groups. Two of the groups (with 99 animals each) received oral applications of DMBA and were either sham-exposed or exposed in a 50-Hz, 100-mG (10 microT) MF for 24 h/d, 7 d/wk, for a period of 91 d. The other two groups (nine animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. The animals were palpated once weekly to assess the development of mammary tumors. At the end of the exposure period, all animals were sacrificed for autopsy and determination of nocturnal melatonin levels in pineal and serum. In controls, DMBA induced palpable tumors in about 55% of the animals within 3 mo after first application. There was a tendency to an enhanced tumor incidence in MF-exposed rats throughout the period of exposure, which, however, was not statistically significant. At autopsy, 60.6% of the sham-exposed and 66.6% of the MF-exposed rats had developed macroscopically visible mammary tumors. Tumor size and tumor burden were similar in both groups. Compared to the groups without DMBA treatment, DMBA-treated rats had significantly lower nocturnal pineal melatonin levels without difference in terms of MF exposure. MF-exposed rats, however, had significantly lower nocturnal melatonin levels in serum than sham-exposed animals. The data demonstrate that although exposure of female rats to a 50-Hz, 100-mG MF significantly decreases circulating melatonin, this is not associated with a significant effect on development or growth of DMBA-induced mammary tumors. In view of the fact that, by using the same model, we recently demonstrated a tumor-copromoting effect of MF exposure at a 10 times higher flux density, the effects of MF exposure on DMBA-induced mammary carcinogenesis appear to be dose dependent.

9,10-Dimethyl-1,2-benzanthracene↗

Exposure of DMBA-treated female rats in a 50-Hz, 50 microTesla magnetic field: effects on mammary tumor growth, melatonin levels, and T lymphocyte activation.

There is growing public concern about the possible health risks, particularly increased cancer risks of exposure to magnetic fields (MF) associated with power distribution systems. Recently, we have started a series of animal studies to investigate this issue, using the DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer in female rats. In the present study, female rats were chronically exposed to a 50-Hz, 50 microTesla (microT) MF with or without DMBA treatment. Because alterations in circulating levels of the pineal hormone melatonin and impaired immune system functions have been involved in breast cancer growth, and both melatonin and immune system are thought to be targets for MF-effects, serum melatonin and the proliferative capacity of splenic lymphocytes were determined in MF-exposed and sham-exposed rats. For this purpose, 216 female Sprague-Dawley rats were divided into four groups. Two of the groups (with 99 animals each) received oral applications of DMBA and were either sham-exposed or exposed in a 50-Hz, 50 microT MF for 24 h/day 7 days/week for a period of 91 days. The other two groups (9 animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. The DMBA-treated animals were palpated once weekly to assess the development of mammary tumors. At the end of the three-month period of MF exposure, the number and size of mammary tumors was determined by autopsy. In controls, DMBA induced tumors in approximately 55% of the animals within the 3 month period of sham-exposure. Already 8 weeks after DMBA application, the MF-exposed group exhibited significantly more tumors than sham-exposed animals. At time of autopsy, significantly more MF-exposed DMBA-treated rats exhibited macroscopically visible mammary tumors than DMBA-treated controls, thus indicating that MF exposure enhances the development and growth of cancers in this model. Comparison of the data from 50 microT with recent data from other flux densities indicated that long-term MF exposure of DMBA-treated rats increases the incidence of palpable and/or macroscopically visible mammary tumors in a highly dose-related fashion. Determination of nocturnal serum melatonin after 9 and 12 weeks of exposure at 50 microT did not yield significant differences between MF-exposed rats and sham-exposed controls, whereas a marked suppression of T cell proliferative capacity was seen in MF exposed rats. The data add further evidence to the hypothesis that hormone-dependent tissues such as breast might be particularly sensitive to MF-effects and indicate that immune system depression is involved in the increased breast cancer growth observed in MF exposed rats.

9,10-Dimethyl-1,2-benzanthracene↗

Afternoon injections of melatonin in the Djungarian hamster Phodopus sungorus: long lasting sex-specific effects and influence of acute treatment on the endogenous pineal melatonin rhythm.

The effects of exogenous melatonin on gonadal function and on the endogenous melatonin profiles of male and female Djungarian hamsters were investigated. Daily afternoon subcutaneous injections of melatonin (50 micrograms) in hamsters kept in long photoperiods (LD 16:8) led to gonadal inhibition in all the treated females (n = 13) but in only 2 of 13 males within the treatment period of 8 weeks (uteri: 244 +/- 11 mg in controls vs. 79 +/- 4 mg in treated hamsters, P < 0.001; ovaries: 13.6 +/- 0.6 mg in controls vs. 7.9 +/- 0.7 mg in treated hamsters, P < 0.001; testes: 1,021 +/- 54 mg in controls vs. 732 +/- 100 mg in treated hamsters, P < 0.05; and accessory glands: 641 +/- 38 mg in controls vs. 548 +/- 70 mg in treated hamsters, P > 0.05). These results indicate that there are some circumstances under which the gonadal responses of the reproductive organs of male and female Djungarian hamsters differ. Interestingly, pineal concentrations of melatonin were found to be significantly higher in males (P < 0.01), possibly indicating a more robust endogenous supply with the hormone, whereas serum melatonin levels were not significantly different between males and females. However, the subcutaneous injection of melatonin (5, 25, and 125 micrograms) exerted no acute effect on the endogenous, circadian melatonin-profile, independent of dosage and sex.

Animals↗

Direct effects of the pineal hormone melatonin on testosterone synthesis of Leydig cells in Djungarian hamsters (Phodopus sungorus) in vitro.

Leydig cells of adult Djungarian hamsters, stimulated with luteinizing hormone (LH), were co-incubated with melatonin at various concentrations in a primary culture system. Testosterone secretion was only affected by melatonin when cells were stimulated with LH. Maximal suppression was observed at low doses of LH (0.5 ng/ml). These effects are at least partially mediated through the adenylate cyclase system, since melatonin was able to reduce forskolin-stimulated testosterone secretion. These results indicate that the time between pulses of LH can be considered to be most highly effective for tonic melatonin actions.

Animals↗

Sustained response of pineal melatonin synthesis to a single one-minute light pulse during night in Djungarian hamsters (Phodopus sungorus).

Previous experiments have demonstrated that short light pulses during the night suppress pineal melatonin formation almost completely for the remainder of the night. Here, the effects of a single 1 min light pulse during the night on melatonin synthesis during the following night was investigated in Djungarian hamsters (Phodopus sungorus). It is shown that the melatonin pattern during the consecutive night is suppressed to a greater extent than that caused by acute light exposure, indicating a very effective light memory of the melatonin-generating neuronal network, possibly a key to understanding the reliability of the photoperiod-measuring system.

Animals↗

Diurnal variations of serum and testicular testosterone and dihydrotestosterone (DHT) in Djungarian hamsters (Phodopus sungorus): testes are the main source for circulating DHT.

Testes and sera of adult Djungarian hamsters kept in a light:dark cycle of 16L:8D were collected every 1.5-3 hr for 24 hr. The concentrations of testosterone (T) and its metabolite 5 alpha-dihydrotestosterone (DHT) were estimated by HPLC separation of the steroids followed by radioimmunoassay. Both testicular and serum concentrations of T and DHT exhibited strong diurnal variations (P < 0.001) with highest levels at the end of the light phase, while both hormones declined drastically during the dark period. The ratios of DHT/T, as an indicator of the activity of the enzyme 5 alpha-reductase, were on average 0.39 in the testes and 0.29 in serum. Comparisons of individual data revealed highly significant correlations between testicular and serum concentrations of the hormones (T:r = 0.87; P < 0.0001; DHT:r = 0.69, P < 0.0001). Likewise, the individual values of testicular and serum DHT/T ratios correlated highly significantly (r = 0.60; P < 0.001). The results indicate that in Djungarian hamsters the main source of DHT is the testes, while the peripheral conversion of T to DHT seems to be negligible.

Animals↗

Characteristics of pulsatile and circadian prolactin release and its variability in men.

In order to investigate the intra- and interindividual variability of spontaneous prolactin (PRL) secretion, 24 h blood sampling at 10 min intervals was performed in ten healthy young men (age 19 to 25 yrs) on three occasions (intervals 2 weeks and 3 months). Plasma PRL concentrations were determined in duplicate by immunoradiometric assay. Peak detection was carried out with the PULSAR program. The circadian rhythm was analyzed by a complex cosinor method combining fundamental (24 h), 1st harmonic (12 h), and 2nd harmonic (6 h) frequencies. The original data was well represented by this calculation as shown by mean (+/- SD) correlation coefficients of 0.84 +/- 0.08. Mean and integrated PRL concentrations showed the lowest intraindividual variability (range 2.8 to 19.6%) of all parameters tested. For the number of peaks per 24 h, a median intraindividual variability of 24.2% (range 6.9 to 50%) was seen. In general, intraindividual variability of parameters of pulsatile PRL release was lower than the variability between subjects. The complex cosinor analysis revealed a bimodal pattern of PRL secretion in most profiles. Acrophases (times of highest PRL levels) were found between 0040 and 1000 h, nadirs between 0030 and 2300 h. The amplitude of the circadian rhythm (Max-Min) ranged from 3.8 to 16.9 ng/ml. The time lag between onset of sleep and acrophase was variable (1.75 to 7.38 hrs). Variability of nadir, minimal and maximal PRL, amplitude, and minimal PRL as percent of the mesor was significantly lower within individuals than between subjects (p < 0.02). During sleep, peak heights and peak amplitudes were significantly higher than during waking periods (p < 0.004). No statistically significant differences were found in the distribution of relative frequencies of peak number, peak amplitudes and peak heights between the three series of profiles. The distribution of peak heights was compatible with a normal distribution. In conclusion, it was shown that the circadian rhythm of PRL secretion in normal men can be analysed accurately and reliably with the complex cosinor method, which is relatively easy to perform and yields results comparable to those obtained by much more complicated programs.(ABSTRACT TRUNCATED AT 400 WORDS)

Activity Cycles↗

Circadian and ultradian variations of pituitary and pineal hormones in normal men: evidence for a link between melatonin, gonadotropin, and prolactin secretion.

The study was performed to investigate the physiological relationship between the pineal hormone melatonin and pituitary functions in normal men. Series of blood samples were obtained at 10-min intervals for 24-hr periods from 10 male volunteers (age 19-25 years). Samplings were repeated after 2 weeks and 3 months. Serum levels of melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone (T) were estimated by immunoassay methods (LH, PRL, every sample; melatonin, every 30 min; T, every 4 hrs; FSH once for each session). Diurnal characteristics of PRL and melatonin profiles were estimated by complex cosinor analysis, while short-term pulsatility of LH and PRL secretion was analyzed by the PULSAR algorithm. Data were correlated by linear regression analysis. The combined information of all three sampling sessions revealed significant negative correlations between the following parameters (N = 10): Amplitude (Ampl) melatonin and Ampl PRL: r = -0.727, P < 0.02; Ampl melatonin and maximal (Max) PRL values: r = -0.73, P < 0.02; Max melatonin and Max PRL: r = -0.725, P < 0.02; area under the curve (AUC) melatonin and Ampl PRL: r = -0.637, P < 0.05; AUC melatonin and Max PRL: r = -0.640; P < 0.05; duration (Dur) of melatonin synthesis and Ampl PRL: r = -0.685, P < 0.03; Dur melatonin and Max PRL: r = -0.676, P < 0.04; Dur melatonin and FSH levels: r = -0.663, P < 0.04; AUC melatonin and LH mean concentration: r = -0.732, P < 0.02; Max melatonin and LH mean concentration: r = -0.657, P < 0.04.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles↗

Breeding of Djungarian hamsters (Phodopus sungorus): influence of parity and litter size on weaning success and offspring sex ratio.

The reproduction of 368 breeding pairs of Djungarian hamsters (Phodopus sungorus) has been recorded and evaluated during 5 consecutive years. Three-hundred-and-eight pairs (= 83.7%) were successful breeders giving birth to 2113 litters (up to 13 per dam) with a total of 12,591 offspring (mean: 6.0 +/- 2.2 [+/- SD] per litter). One-hundred-and-fifty dams delivered within 25 days after pairing, indicating a breeding success in the first oestrous cycle of 40.8% of all pairs (95% confidence interval: 35.7%-46.0%). The average number of offspring was higher in the 2nd than in the first litter, reaching a maximum in the 3rd (6.8 +/- 2.0), and decreasing thereafter. The loss of offspring (mean: 24.2%) was higher in older parents and influenced by the number of offspring per litter, indicating that experience and stress contribute to breeding success. A small, but significantly higher number of females was recorded only when no loss of offspring occurred until weaning (females: 2.36 +/- 1.75; males: 2.16 +/- 1.63, P < 0.001). There was no indication of a shift of the offspring sex ratio towards favouring females with increased litter numbers, in contrast to the predictions of the Trivers-Willard hypothesis, at least with respect to the species and the breeding conditions as described in this report. Since all breeders were kept under long-day type photoperiods (16L:8D), no signs of seasonality in breeding outcome were noted.

Animals↗

The adult human cerebellum is a target of the neuroendocrine system involved in the circadian timing.

In an investigation aimed at comprehensive mapping of the adult human brain with respect to receptor sites for the pineal hormone melatonin, we consistently observed specific binding in the cerebellum. Autoradiography and in vitro binding analysis with 125I-labeled melatonin were used to examine the location and the properties of these binding sites. In all cerebellar lobes, highest-density specific binding was localized to the external zone of the molecular layer. The binding was rapid, saturable, displaceable, specific and of high affinity. Physiological concentrations of NaCl decreased the affinity, while presence of calcium ions promoted it. The non-hydrolyzable GTP analog, GTP gamma S, inhibited binding in a dose-dependent manner and provoked a shift towards low affinity. The results strongly suggest that these binding sites may be functional melatonin receptors, and indicate that the adult human cerebellum is a target of melatonin, the pineal hormone involved in the control of the circadian timing.

Adult↗

Increased oxidation of pineal serotonin as a possible explanation for reduced melatonin synthesis in the aging Djungarian hamster (Phodopus sungorus).

Groups of young adult (1.7 months) and old adult (9.7 months) female Djungarian hamsters were exposed to short-day photo-periods (SD; 8L:16D) or long-day photoperiods (LD; 16L:8D) for 6 weeks. Pineal and serum melatonin rhythms were dampened in old SD animals when compared with young SD animals. The melatonin precursor serotonin showed diurnal variations with opposite phases to melatonin synthesis. However, pineal serotonin levels were even lower in old SD animals than in young SD animals, contrary to the expected accumulation of the precursor. The synthesis of a metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), was significantly lower in younger hamsters, under both photoperiods. These results indicate that the age-associated decline in the production of melatonin is a consequence of an increased oxidation of its precursors.

Aging↗

Photoperiodic responses in Djungarian hamsters (Phodopus sungorus): importance of light history for pineal and serum melatonin profiles.

Male Djungarian hamsters with previous light experience of long photoperiods of 16 h of light per day (16L:8D) or short photoperiods (8L:16D) were transferred either to the opposite photoperiods or to intermediate photoperiods (14L:10D). It was demonstrated that the same intermediate photoperiod could exert inhibitory or stimulatory effects on coat color, body weight, and the reproductive system, dependent on the previous light history. The response was graduated in accordance with the degree of change in day length. Despite opposite responses to the same photoperiod, diurnal patterns of melatonin in the pineal glands were identical. However, the circadian melatonin pattern in serum of photoinhibited hamsters had a more pronounced nighttime elevation than that found in the serum of photostimulated animals. In hamsters nonresponsive to short photoperiods, no proper short-day pattern was found. Melatonin production is a highly dynamic process, causing concentration shifts in the pineal gland and changes in the serum amplitude during prolonged exposure to short photoperiods. The different reactions to identical photoperiods are associated with different serum melatonin patterns, as shown here for the first time.

Animals↗

Reliable analysis of individual human melatonin profiles by complex cosinor analysis.

The analysis of diurnal secretion patterns of the pineal hormone melatonin should provide information about magnitude of peak concentration, time of peak (acrophase), and duration of elevated hormone levels. We report here on a method for analysis of human melatonin secretory rhythms which fulfills these requirements with considerable precision. Blood samples were obtained from 10 healthy male volunteers at 30 min intervals throughout a 24 hr period, three times (the initial blood sampling was repeated after 2 weeks and 3 months). These sets of 48 plasma samples per volunteer were analyzed for melatonin by radioimmunoassay. The mean intra-assay variation was 10.3%, and inter-assay variations were 15.8% at 21 pg/ml, 11% at 28 pg/ml, and 9.4% at 48.6 pg/ml. Data were subjected to single cosinor analysis (SCA) or analyzed by a complex cosinor analysis (CCA) with the fundamental and the first harmonic as parameters. Both methods provided essentially the same information about the acrophases, whereas the CCA had a clear advantage in terms of better regression coefficients between the original data points and the calculated curve (CCA: r = 0.952 +/- 0.018; SCA: r = 0.867 +/- 0.039 [means +/- SD]; P < 0.001). As a consequence, maximum and minimum values and the times of onset and cessation of melatonin production could be estimated easily and reliably without the need for rough and/or subjective measures. By comparing the three sampling sessions, the secretory rhythm of each individual was clearly reproducible (mean coefficient of variation 8.4%), thus confirming earlier work. Interindividual differences, however, were quite pronounced, especially with respect to amplitudes (more than 25% coefficient of variation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗