Endokrinologie最新文献

Chronic administration of norethisterone for 75 days caused a marked inhibition of the pineal gland activity of cycling albino rats. In addition to a decrease in the nuclear diameter, possibly the cell size also decreased. The progestin, however, failed to induce mitosis in this gland. It is suggested that prolonged administration of norethisterone exerts untoward effects on the pineal gland function in adult female albino rats.

To examine the direct effects of cyproterone on the ovarian biosynthesis of steroids, tissue slices obtained from two cyclically functional human ovaries were incubated with [4-14C]pregnenolone as precursor. The steroid production was determined by measuring the concentration of eleven 14C-labelled steroids in the medium at the end of a 3-h incubation. Under control conditions, the in vitro-synthesis of 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol (5-ene-3 beta-hydroxy-steroids) and androstenedione represents the characteristic profile of steroids of the ovary from the follicular phase. The addition of cyproterone to the incubation medium inhibited the biosynthesis of androstenedione, whereas 17 alpha-hydroxypregnenolone and dehydroepiandrosterone increased. The in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, oestrone and oestradiol-17 beta represents the characteristic profile of steroids of the luteal ovary. The biosynthesis of progesterone, 17 alpha-hydroxyprogesterone and oestradiol-17 beta is inhibited by cyproterone. The principal manifestation of the effects of cyproterone on the two different profiles of steroids is an apparent inhibition of the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase activity. It is noteworthy, that the effects of the "pure antiandrogen" cyproterone are similar to those effects previously published for progestagens (chlormadinone acetate, norethisterone acetate and D-norgestrel). A simplified concept of the direct effects of cyproterone and progestagens on the steroidogenesis in the human ovary is proposed. The results indicate, that cyproterone, in addition to its well-known androgen receptor blocking effect, act directly on the steroid biosynthesis in the human ovary in vitro.

The close relationship between C19O2 steroid excretion and the ratio of C19O2/C21O5 steroids indicates that it is the elevation of C17,20-lyase activity, which represents the decisive factor in the cessation of androgen-corticoid disproportion during the puberty of healthy children. In 3-6 year-old C21-hydroxylase deficient children treated with corticoids in doses only partially suppressing endogenous ACTH secretion, the excretion of total C19 steroids increased continuously parallel with a well defined elevation of 16 alpha-oxygenated-C21 steroid excretion. The patients did not show the physical signs of adrenarche before six years. This can be attributed to three factors: a) substitutional corticoid therapy; b) intraglandular control of delta 5-pathway by 16 alpha-hydroxylation of C21 steroids; c) neutralisation by 11 beta-hydroxylation of the androgen effect of C19O2 steroids.

Male Wistar rats with an average age of 28 weeks received diets high (HFD: 50% fat) or low (LFD: 3% fat) in fat content. Rats were restricted on iodine intake by feeding pure diets without iodine addition. The relative degree of iodine shortage of rats was estimated by 131I-uptake. PB131I and ETR. Serum cholesterol, whole body lipid content and liver deiodinase activity of LFD (control)- and HFD-rats were analyzed. A change of diet feeding from high to low fat content and vice versa took place to discriminate the effect of diet fat from body fat content of rats on serum cholesterol and deiodinase activity. HFD fed rats with high body fat content showed at iodine restriction the same serum cholesterol concentration as relative lean LFD-animals. Post feeding change from diet rich to poor on fat and vice versa at 4 weeks the obese animals have lost body fat only 10-20% at calorie restriction and exhibit higher serum cholesterol levels and equal liver deiodinase activity as lean, now fat rich fed control animals. Heavy HFD-rats fed on fat rich diet for 22 weeks have approximately two times higher liver lipid content as light LFD-animals. Because liver lipid content and deiodinase activity between light LFD- and heavy HFD-rats before and after change of diet feeding are equal, a relation between liver lipid content and enzyme activity is discussed.

An insulin-deficient diabetes of long duration was induced by intravenous injection of alloxanmonohydrate (200 mg/kg and 100 mg/kg body mass, respectively) in 23 pigs (Landrace, Duroc) of 20-44 kg body mass. The dose of 200 mg/kg body mass was too high and there were fatal outcomes only. With the dose of 100 mg/kg and an initial body mass of 30-35 kg it is possible to induce a chronic diabetes mellitus in the pig. As complications we observed intoxications caused by alloxan, hypoglycemic situations from the 6th hour after application of alloxan with possible hypoglycemic damages, and septic complications by the intravenous catheter. Five out of 23 animals are still alive, 2 animals for 31 months and the others for 19 months. All the living animals have plasma glucose levels between 11 and 17 mmol/1 with very low values of plasma insulin. The serum triglycerides increased slightly in some cases, but not the serum cholesterol. The weight gain is retarded.

Levels of 17 alpha-hydroxyprogesterone were estimated by radioimmunoassay in 174 amniotic fluid specimens obtained from 162 normal pregnancies of 16-20 weeks gestation. Another 18 specimens from 11 normal pregnancies between 25-42 weeks gestation and 7 specimens from 7 women who each previously had given birth to a child affected with CAH were also studied. There was no sex difference in AF 17 alpha-OH-progesterone levels, nor any significant downward trend in concentrations throughout the observed gestation period. Among the 7 subjects with previous history of CAH offsprings, 4 demonstrated normal levels of AF 17 alpha-OH-progesterone and 3 significantly higher values. HLA-typing of the cultivated amniotic cells confirmed these 4 cases to be heterozygous for 21-hydroxylase deficiency. The three subjects with high AF 17 alpha-OH-progesterone levels delivered babies affected with CAH, although HLA-typing in one case was non-conclusive. The failure of HLA-typing in 1 case for a confirmatory diagnosis indicates that the prenatal diagnosis of CAH must continue to rest on joint endocrinological and genetical investigations.

A procedure is described for determining salivary cortisol levels by a competitive protein-binding assay using horse transcortin. The collection of saliva was performed by means of filter paper-strips. Filter paper samples are more than 5 days stable after air-drying. In this form, the samples could be stored without refrigerator or deep-freezer and, if necessary, sent by post to the laboratory without any special precaution. Stressful situation of either painful or anxious origin were associated with an adequate increase of salivary cortisol levels. The increases were 157 to 230% of the initial or normal values dependent on the kind of stress. The mean values in 4 cases of Cushing's syndrome were 380% and 1 hour after 25 I.U. ACTH 690% higher than those in normal persons. In normal persons, a well-defined circadian rhythm has been observed.

The effect of addition of human follicular fluid to cultures of granulosa cells of large sheep follicles (4-6 mm in diameter) on basal and LH-stimulated progesterone secretion was investigated. Both luteinization and progesterone secretion were inhibited by addition of 10% (w/v) charcoal-treated follicular fluid from medium (2-6 mm) and large (7-16 mm) follicles which had low concentrations of estradiol-17 beta, progesterone and LH. In comparison, the fluid from large follicles, having high levels of the same hormones, stimulated both the parameters, and addition of LH along with the fluid had no further effect. Fluid collected from cystic follicles appeared to be stimulatory which also had elevated levels of estradiol-17 beta and progesterone. These findings indicate the presence of both the inhibitors and stimulators of luteinization in human follicular fluid. The effectiveness of any of them either to inhibit or stimulate luteinization probably will depend upon the composition of the follicular fluid and the stage of maturation of the follicles from which it was collected.

The authors investigated the effect of one-week administration of verapamil in daily therapeutic doses of 4 X 40 mg by the oral route and the effect of nifedipine in daily therapeutic doses of 3 X 20 mg by the oral route. Verapamil and nifedipine did not affect significantly the levels of thyrotropin, triiodothyronine and thyroxine nor their response after stimulation with TRH. The theoretical and practical impact of this finding is discussed in particular with regard to possible side-effects of calcium antagonists during their therapeutic use in clinical cardiology.