Microbial transformation of steroid

When studying the transformation reactions of Δ⁴-3-ketosteroids of the pregnane series by strains ofStreptomyces fradiae, 6β-hydroxy-or 6β, 11α-dihydroxy-derivatives were found to be the main metabolites. From the aspect of the taxonomy of Actinomycetes, these reactions can be utilized in classification of the species, since study of different strains ofStreptomyces fradiae showed that this property is stable and that it is characteristic for the given species.     

Mechanisms of steroid resistance

A method is described for the rapid determination of binding capacity and subcellular distribution of radioactive dexamethasone by cultured lymphoma cells. Using it, a number of steroid-resistant lymphoma cell clones were shown to be deficient in steroid binding to specific cytoplasmic receptors (r-) in transfer of the receptor-steroid complex to nuclei (nt-), or in the reactions subsequent to nuclear localization of the complex (d-). The relative proportions of those types of variants were determined in a steady-state population. About 80% were r-, and the remainder were equally divided between nt- and d-. Quantitative steroid-binding experiments suggest that certain receptor-containing variants possess altered receptor molecules.     

Genetic heterogeneity of steroid sulfatase deficiency revealed with cDNA for human steroid sulfatase

Three cDNA clones with inserts of 1.2-1.6 kb that reacted both with antibodies and oligonucleotides specific for steroid sulfatase were isolated from a human placental library in lambda gt11. The 5'-end of one of the inserts, STS-3, was sequenced and colinearity with the amino acid sequence of 3 peptides of steroid sulfatase encompassing 64 amino acids was demonstrated. STS-3 hybridized with 2.5, 4.6 and 6.3 kb species in poly(A)+RNA and with 2.5, 4 and 9 kb fragments of EcoRI digested human DNA. The frequency of the EcoRI fragments in DNA from females was approximately twice that in DNA from males. DNA from two patients with steroid sulfatase deficiency and X-linked ichthyosis did not hybridize with STS-3. DNA from a third patient showed a normal hybridization pattern. It is concluded that steroid sulfatase deficiency is a genetically heterogenous disorder.     

Time-resolved fluoroimmunoassay of steroid hormones

The use of europium chelates as labels in immunoassays and their sensitive quantitation based on time-resolved fluorescence is reviewed. The technique is applied on competitive solid-phase immunoassays for direct determination of progesterone and estradiol in serum samples. Both antigen- and antibody-labelled competitive assays are described. The nonisotopic label technology, which provides a very high specific activity, as well as the antibody-labelled competitive assays, present several advantages in the assay of haptens as e.g. steroids. As the optimal sensitivity of competitive methods is not limited by the specific activity of the label the steroid assays which employ europium chelates as labels do not show any marked increase in sensitivity as compared to that achieved by using 125I. The potential sensitivity provided by the high specific activity of the label is optimally utilized in noncompetitive immunometric assays.     

Sex steroid regulation of autoimmunity

The immune response of males and females is not identical but instead has been shown to be dimorphic in its nature, with females generally demonstrating a greater overall response than males. This dimorphism extends to both the humoral and cell mediated systems and appears to be mechanistically based on the differences in type and concentration of sex steroids in males vs females. Furthermore, growth hormone and prolactin secretions which are different in males and females may also be partly responsible for the observed dimorphism. Because autoimmune disease results from a pathological perturbation of normal immune function, it follows that expression of these disease will also demonstrate a dimorphic pattern. Examples of this autoimmune dimorphism include (but are not limited to) lupus, rheumatoid arthritis and multiple sclerosis with the two former more prevalent in females than males and the latter more severe during pregnancy. To explain autoimmune dimorphism it therefore becomes necessary firstly to describe the cellular and hormonal interactions found in normal immune regulation and thereafter extrapolate these to autoimmune phenomena.     

Nongenomic actions of steroid hormones

Steroid hormones modulate many physiological processes. The effects of steroids that are mediated by the modulation of gene expression are known to occur with a time lag of hours or even days. Research that has been carried out mainly in the past decade has identified other responses to steroids that are much more rapid and take place in seconds or minutes. These responses follow nongenomic pathways, and they are not rare.