Cortisol and cortisone production in rat and mouse adrenal incubations

The presence of 17 alpha-hydroxylase in rodent adrenals is debated. The presence in blood of mice of 11-deoxycortisol together with the absence of cortisol is well known. We demonstrated here the in vitro synthesis of 17 alpha-hydroxyprogesterone and cortisol from [3H]progesterone in rat and mouse adrenals. We have shown that these syntheses represented 45 and 28% of those of 11-deoxycorticosterone and corticosterone, respectively, from progesterone. These data clearly suggest the presence of a 17 alpha-hydroxylase activity in vitro in these rodents adrenals. In addition, a noticeable synthesis of cortisol (0.87-1.57% per mg tissue, i.e. 52-64% per incubation flask) from 11-deoxycortisol was also observed and was inhibited by 0.1-0.3 mumol of Metyrapone and SKF 12185. These results allow to underline that the adrenals of rat and mouse, two species commonly used in laboratory experiments, may be used for in vitro investigations on cortisol metabolism from exogenous radioactive precursors.     

An auxin-auxotrophic mutant of Nicotiana plumbaginifolia

Summary Auxin (indole-3-acetic acid) is considered to be an important signalling molecule in the regulation of plant growth and development but neither auxin synthesis nor its mode of action is clearly understood. To identify genes involved in these processes, mutations were sought that altered the auxin requirement of plant tissues for growth. For the first time mutant plants were obtained that carry a recessive mutation at a single nuclear locus (auxl) which results in an absolute requirement for exogenous auxin for normal growth. In the absence of auxin treatment, mutant plants undergo premature senescence and die.Abbreviations BAP 6-benzylaminopurine - BUdR 5-bromodeoxyuridine - 2,4-D 2,4-dichlorophenoxyacetic acid - FUdR 5-fluorodeoxyuridine - IAA-EE indole-3-acetic acid ethyl ester - IMS indole-3-methanesulfonic acid     

Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol

17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis. This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione. Indeed, our data show that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone. This fact allowed us to infer that this new pathway is closely related to the activity of the 11 beta-hydroxylase that is responsible for the synthesis of cortisol. Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals. This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.     

Magnesium: metabolism and hormonal regulation in different species

1. The magnesium ion is of great importance in physiology by its intervention in 300 enzymatic systems, its membrane role and its function in neuromuscular excitability. 2. The skeleton is the first pool of magnesium in the animal body. 3. For intestinal absorption, renal metabolism, bone accretion and resorption, magnesium shows analogies with calcium. 4. Magnesium exchange between extracellular, cellular and skeletal compartments are very precisely controlled. 5. Parathyroid hormone, 1 alpha, 25-dihydroxy-vitamin D3, calcitonin and estrogens are the principal hormone systems implicated in magnesium metabolism. 6. The kidney is the principal site of magnesium excretion and shows important magnesium regulation mechanisms.     

Susceptibility of platelet alpha-actinin to a Ca2+-activated neutral protease

Purified alpha-actinin from human platelets was digested with Ca2+-activated protease from muscle. The alpha subunit (Mr = 100 kDa) was degraded into a unique polypeptide b of slightly lower molecular mass. In fresh platelets, only the a subunit was detected by immunoblotting techniques, while in out-dated platelets, both a and b polypeptides were present. Since a similar conversion of a to b occurs in vitro as in whole platelets, it can be assumed that, in platelets, alpha-actinin is cleaved by the endogenous Ca2+-activated protease.     

Trichinosis: Thiabendazole in the Treatment of 11 Cases

We have studied 11 cases of acute human trichinosis; five of these patients were treated with thiabendazole. We have reviewed the laboratory data for these patients and described their course. This study has failed to show any definite effect of thiabendazole on the course of human trichinosis at the doses used. However, thiabendazole may have decreased the infectivity of the larvae which were embedded in the muscles of our patients.     

Influence ofl-thyroxine,l-triiodothyronine,thyroid stimulating hormone,or estradiol on the cell kinetics of cultured mammary cancer cells

Summary We describe the in vitro influence of 3,5,3′-triiodo-l-thyronine (T₃),l-thyroxine (T₄), a thyroid-stimulating hormone (TSH), and/or estradiol (E₂: chosen as the control of the methodology) on the cell kinetics (cell distribution in the S+G₂+M phases) of mouse MXT and human MCF-7 mammary cancer cells. Experiments were performed by means of a cell image processor, analyzing MCF-7 or MXT cells that had been grown on glass cover slips and whose nuclei had been stained by the Feulgen reaction, which is selective and quantitative (stoichiometric) with respect to DNA. We show that T₃, T₄, and TSH at 0.01 μM dramatically stimulate the cell kinetics of the MXT mouse and the MCF-7 human mammary cancer cell lines. Indeed, the three hormones bring about a significant transient increase in the S+G₂+M fraction as does E₂. Furthermore, our data indicate that E₂ and TSH are antagonistic with regards to MXT or MCF-7 cell kinetics. This work is supported by grants awarded by the IRSIA and the Fonds de la Recherche Scientifique Médicale (FRSM, Belgium).     

Internal desynchronization of circadian rhythms and tolerance of shift work

Fifteen male subjects including 12 shift workers (oil refinery operators) volunteered to document circadian rhythms in sleep-wake, grip strength of both hands, peak expiratory flow, heart rate, self-rated drowsiness, fatigue and attention. Each of these variables was measured 4 to 6 times/day for 2 to 3 weeks. In addition, both axillary temperature (with a shielded probe) and wrist activity were almost continuously recorded at 15 min intervals during the same time span. Individual time series were analyzed according to several statistical methods (power spectrum, cosinor, chi 2, etc.), in order to estimate the prominent circadian period tau and to evaluate both individual and subgroup differences with regard to tolerance of shift work, age, duration of shift work. The present study confirms for continuously recorded temperature and wrist activity, grip strength of both hands, heart rate and peak expiratory flow that intolerance of shift work is frequently associated with an internal desynchronization. However, this conclusion cannot be extended to circadian rhythms in self-rated drowsiness, fatigue and attention. The internal desynchronization among several circadian rhythms supports the hypothesis that these latter are driven by several oscillators, with presumable differences between right and left hemispheres as suggested by unequal values of tau in rhythms of both hand grip strength. Since an internal desynchronization can be observed in tolerant shift workers having no complaint, it is likely that symptoms of intolerance are related to the subject's sensitivity to internal desynchronization rather than to the desynchronization itself.     

Analysis of phytochrome- and ABA-deficient mutants suggests that ABA degradation is controlled by light in Nicotiana plumbaginifolia

The phytochrome chromophore-deficient mutant, pew1, of Nicotiana plumbaginifolia exhibited decreased germination and slower dehydration of detached leaves during water stress as compared with the wild-type. These physiological processes are controlled by abscisic acid (ABA) and we examined, therefore, whether phytochrome plays a specific role in the regulation of ABA metabolism using the pew1 mutant. The ABA contents of mature seeds and young leaves were analysed and in both cases mutant material was found to contain higher amounts of ABA as compared with the wild-type. This indicates that the phytochrome activation can lead to a decrease of the ABA level in the wild-type plant. The role of phytochromes was investigated in greater detail using the ABA-deficient mutant aba1 of N. plumbaginifolia exhibiting an early and synchronous germination. This mutant accumulates at very high levels a metabolite derived from a precursor (ABA-aldehyde) in the ABA biosynthetic pathway. The first biochemical characterization of this molecule, which corresponds to the glucose-conjugated ABA-alcohol (ABA-AG) is described. A pew1-aba1 double mutant exhibiting both an etiolated growth and early germination was also obtained. The comparable accumulation of ABA-AG in the pew1-aba1 double mutant as compared with the aba1 mutant allowed the proposition that, in a wild-type plant, the phytochrome-mediated light signal enhances ABA degradation rather than inhibits its biosynthesis.