Dehydroepiandrosterone modulates the spontaneous and IL-6 stimulated fibrinogen production of human hepatoma cells.

The role of an androgen, dehydroepiandrosterone (DHEA) has been studied on the constitutive and IL-6 induced fibrinogen production of HepG-2 cells. DHEA markedly augments the constitutive fibrinogen production of the hepatoma cells in a dose dependent fashion. Oppositely, for IL-6 induced fibrinogen production, DHEA is strongly inhibitory. The effectiveness of DHEA on the constitutive fibrinogen production is further potentiated if the hepatoma cells are preincubated with a glucocorticosteroid, dexamethasone. These findings demonstrate that the complex interaction between the steroid- and cytokine-directed regulation of the production of acute phase proteins is further coloured by the action of androgens on immune and hormonal systems.

Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2.

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.

Serum steroid hormone levels in systemic lupus erythematosus (SLE).

Dehydroepiandrosterone (D), D sulphate (DS), testosterone (T) and oestradiol (OE2) were determined by radioimmunoassay; cortisol (F) by a spectrofluorimetric method in the serum of 54 female patients with SLE. The values were evaluated in two age groups (32 patients with active ovarian function and 22 in menopause). The serum cortisol, T and DS levels were decreased, and there was no difference in that of free (unconjugated) D and OE2 concentrations compared to normal female subjects.

Interrelationship between the immunological and steroid hormone parameters in rheumatoid arthritis.

In the present work the correlation between the immunological parameters and plasma androgen hormone levels in rheumatoid arthritis (RA) was examined. Female patients were divided in groups according to their age and immunologic state. Plasma dehydroepiandrosterone (D), D sulphate (DS), and testosterone (T) levels were determined by radioimmunological methods. The values were related first to those of normal controls. The T and DS levels were significantly decreased in all patient groups examined, the D level was low only in "Rf+ active" state aged 18 to 45 years. Furthermore, it was examined whether the decreased hormone levels were in relationship either with the autoantibody (Rf) formation or with the activity of the disease. According to the observations the T levels were influenced neither by the autoantibody formation nor by the activity of the disease. The DS and D levels appeared to correlate both with the autoantibody formation and the activity of the disease, particularly in young patients, being significantly low in the "Rf+ active" state. From these we concluded that the condition of the immune system has an influence on the sex hormone and/or adrenal androgen function.

Plasma dehydroepiandrosterone, dehydroepiandrosterone sulphate and androsterone sulphate levels and their interaction with plasma proteins in rheumatoid arthritis.

Female patients with rheumatoid arthritis (RA) in Steinbrocker's II and III rating scale have been examined. They were without steroid treatment at least six months before observation. Plasma protein picture showed hypoalbuminaemia and hyperglobulinaemia. There was no difference relative to controls either in the total (free + protein bound) plasma dehydroepiandrosterone (D) level, or in its distribution with plasma proteins. In the age group of 18 to 45 years, a statistically significant decrease have been observed in the total plasma dehydroepiandrosterone sulphate (DS) level without any change in its distribution in protein binding. Furthermore, low androsterone sulphate (AS) levels were found irrespective of the age of patients. The results gave further information on the pathomechanism resulting in an abnormal androgen hormone pattern of blood and a low metabolite excretion, observed previously in patients with RA:.

Effect of dehydroepiandrosterone on hereditary angioedema.

Hereditary angioneurotic edema (HAE) is a complement-related clinical disorder with a deficiency of the C1 esterase inhibitor protein. Eight patients with severe attacks of the disease were treated with the adrenal "androgen" dehydroepiandrosterone sulphate (DS). Steroid therapy for 3-28 months resulted in dramatic improvement in their clinical state and a moderate increase in the serum concentration of C1 inhibitor. There was a significant increase in the serum level of either unconjugated dehydroepiandrosterone (D) or of DS during treatment.

Adrenocortical function in bronchial asthma.

Female patients with "intrinsic" bronchial asthma without corticosteroid therapy for at least 3 months revealed low blood concentration of total protein-unbound + protein-bound) and free (biologically active, protein-unbound) cortisol, dehydroepiandrosterone and dehydroepiandrosterone sulphate, as also a low urinary excretion of dehydroepiandrosterone metabolites. The results suggest that bronchial asthma is associated with hypoadrenia due to an impaired production not only of cortisol, but also of adrenocortical androgens resulting in an insufficient hormone supply of the target organs. These seem noteworthy, since recent observations showed relationships between the immune responsiveness and sex hormones.

Protein-corticosteroid interactions in peripheral plasma and synovial fluid of patients with rheumatoid arthritis and osteoarthrosis.

The individual protein fractions, together with the unbound (biologically active) and specifically globulin-bound 11-hydroxysteroids, were determined in the plasma and synovial fluid of patients with rheumatoid arthritis (RA). The values were compared with those measured in control subjects and in patients with severe osteoarthrosis (OA). Hypoalabuminaemia and hyperglobulinaemia, as well as an increase in the unbound and a decrease in the specifically bound corticosteroids were found in the plasma of the RA patients. The protein and corticosteroid levels were lower, and the level of the protein-bound corticosteroid fraction higher, in the synovial fluid than in the plasma. Significant differences between the RA and OA patients in respect of these parameters were also observed. The findings indicate that the altered hormone pattern is not a nonspecific result of the permanent stress situation to which RA patients are subjected. They point out the existence of a fairly specific but still unknown mechanism that compensates the high level of unbound corticosteroids, thus accounting for the absence of any clinical signs of hypercortisonism.

Free and solvolysable dehydroepiandrosterone and androsterone in blood of mammals under physiological conditions and following administration of dehydroepiandrosterone.

A gas chromatographic method has been empolyed for the determination of dehydroepiandrosterone (D), androsterone (A), dehydroepiandrosterone sulphate (DS) and androsterone sulphate (AS) in the peripheral blood of human subjects and in various mammals under physiological conditions and after the administration of D or DS. Unconjugated D has been isolated and the resting level determined in the rat, rabbit, dog , sheep, pig and cow, while DS was detectable in the peripheral circulation of the rat, dog and pig. Unconjugated A was present in blood of the rodents and domestic ungulates studied, while the parent sulphate could be demonstrated only in rat, dog, pig and cow. The plasma of lower mammals contained D in higher (0.8-10.9 microng/100 ml) and DS, if any, in lower level (1.5-5.7 microng/100 ml) than the human plasma samples (0.1-2.7 and 86-308 microng/100 ml, respectively). There was a more pronounced increase in D and A than in the DS and AS level in the rat and dog following administration of D. On the contrary, exogenous D hardly affected unconjugated D and appreciably enhanced the DS level in human plasma. The conclusion drawn for human subjects, that D is the metabolically active and DS the reserve hormone, does not seem to be valid for all the animals here studied.

A simple gas-liquid chromatographic method with electron capture detection for the determination of progesterone in the blood of humans and domestic animals.

A simple routine method is reported for the determination of progesterone in blood by gas-liquid chromatography. An unlabelled internal standard, testosterone acetate, was added to plasma samples. Following preliminary purification by thin-layer chromatography, progesterone in pregnancy plasma was evaluated as the free steroid with a flame ionization detector. The hormone in the plasma of women during the menstrual cycle and of cycling domestic animals was determined as the 3-enol ester heptafluorobutyrate by electron capture detection. The validity of testosterone acetate as an internal standard was proved by simultaneous processing of [7alpha-3H]progesterone and a [4-14C]testosterone acetate and the determination of the isotope ratio in samples. The results of control experiments and normal values are also presented.