A.J.M. Vermorken

The antiandrogenic effect of progesterone on the hamster flank organ

Progesterone, topically applied, prevents the stimulation of the hamster flank organ by testosterone, but not by dihydrotestosterone. 5α‐Dihydroprogesterone does not prevent stimulation by either of the two androgenic hormones. Neither progesterone nor 5α‐dihydroprogesterone stimulate the flank organ to any extent.

Metabolism of benzo[a]pyrene in isolated human scalp hair follicles

Human scalp hair follicles contain an enzyme system that metabolizes the carcinogen benzo[a]pyrene. The major ethyl acetate soluble metabolites are 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene,9,10-dihydro-9,10-dihydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. Addition of 1,1,1-trichloropropene-2,3-oxide (TCPO), an inhibitor of epoxide hydratase, prevents the formation of the dihydrodiols. The overall metabolism can be inhibited by the addition of alpha-naphthoflavone. The metabolism of benzo[a]pyrene in a cell culture of human scalp hair follicles has also been investigated. The results show that the activity of arylhydrocarbon hydroxylase (AHH) and epoxide hydratase (EH) is maintained in culture.

An improved method for evaluating antiandrogens

SummaryIn recent years, the hamster flank organ test has been frequently used to screen compounds for antiandrogenic activity. When used routinely, the diameter of the pigmented spot is used to evaluate the androgenic or antiandrogenic effect of the drug tested. In this article, it is shown that the pigmented spot and the sebaceous glands may respond to a quite different degree to hormonal stimuli, indicating that visual observation alone is insufficient for screening purposes. Determination of sebaceous gland sizes by histochemical techniques allows a better evaluation of androgenic or antiandrogenic effects.

A method for the evaluation of the local antiandrogenic action of 5α-reductase inhibitors on human skin

A method has been developed for the first time that allows the evaluation of the effect of therapeutic concentrations of 5α‐reductase inhibitors in human skin, without applying radioactivity to the skin. Moreover, the method makes it possible to determine whether inhibition is found only at the application site or also in other parts of the skin.

Fabry's disease: biochemical and histochemical studies on hair roots for carrier detection

A method to assay α‐galactosidase and acid phosphatase activities in single hair roots is described. Enzyme histochemical studies show that the distribution of acid phosphatase in the human hair root matches that of α‐galactosidase. Histochemically, the main activity is located in the upper part of the sheath near the orifice of the duct of the sebaceous gland. This is confirmed by enzyme assays on different parts of the hair root after dissection. The variation in the values found in individual hair roots is improved by relating α‐galactosidase to acid phosphatase activities. Storage experiments indicate a remarkable stability of both α‐galactosidase and acid phosphatase in human hair roots.

Dedifferentiation of lens epithelial cells in tissue culture.

Lens epithelial cells can be kept in their original differentiated state or brought to dedifferentiation depending on the culture conditions. The different stages of differentiation can be identified using specific markers, namely the activity of steroid metabolizing enzymes, and the synthesis of specific structural lens polypeptides. For this reason lens epithelial cells in tissue culture provide a unique system for the study of the regulation of RNA and protein biosynthesis.

Hydroxylation of dehydroepiandrosterone in human scalp hair folhcles

The dehydroepiandrosterone hydroxylatmg enzyme system in the hair follicle has been characterized. It is found in the particulate fraction of the follicle, and is inhibited by carbon monoxide and the cytochrome P450 inhibitor metyraponc, and appears to be dependent upon NADPH. In these major characteristics the hair follicle enzyme is very similar to the liver monooxygcnase system.

Effect of impaired glycosylation on the synthesis of envelope proteins of rauscher murine leukemia virus

Abstract The effects of 2-deoxy- d -glucose (deoxyglucose) and cytochalasin B on the synthesis of Rauscher murine leukemia viral envelope proteins were investigated. JLS-V9 cells infected with and producing Rauscher murine leukemia virus (R-MuLV) were cultured in the presence of deoxyglucose (15 m M ) or of varying concentrations of cytochalasin B (0.1–25 μg/ml) and the synthesis of virus-specific polypeptides was examined in pulse-chase experiments. Overall protein synthesis was inhibited to some extent by cytochalasin B; at a concentration of 25 μg/ml an inhibition of about 70% was observed. Incorporation of d -[1- 3 H]glucosamine, however, was almost completely inhibited (97%) at the same concentration of the drug. Newly formed virus-specific polypeptides were analyzed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis after immuno-precipitation with polyvalent and monospecific antisera against R-MuLV proteins. No specific effect on the synthesis of the gag gene product p30 was observed. The synthesis of the precursor of the envelope polypeptides, env -pr82, however, was prevented in the presence of cytochalasin B. Instead, the synthesis of a new glucosamine-deficient 70,000-molecular weight polypeptide ( env -pr70 ∗ ) was observed. Env -pr70 ∗ could be immunoprecipitated with anti-gp69/71 serum and anti-p15(E),p12(E) serum and, therefore, probably represents the protein moiety of env -pr82. In pulse-chase experiments in the presence of cytochalasin B, env -pr70 ∗ was converted to a polypeptide with a molecular weight of about 75,000 which was slowly lost during the chase period. Production of virus-specific gp69/71, p15(E), and p12(E) was inhibited under these conditions. Similar results were obtained with deoxyglucose, except that the inhibition of glycosylation by the latter compound is irreversible.

Hydroxylation of dehydroepiandrosterone in the eye lens

Hydroxylation of the steroid hormone dehydroepiandrosterone in the calf lens is inhibited by carbon monoxide and stimulated by NADPH. The enzyme concerned was found to be membrane-bound. Although the enzyme resembles the liver mono-oxygenase system in these characteristics, the presence of cytochrome P-450 in the lens could not be proved by measuring a difference spectrum with carbon monoxide, probably because the concentration of the enzyme is too low. Preparations of purified lens fiber plasma membranes also hydroxylate dehydroepiandrosterone. This indicates that the fiber plasma membranes act as supports for enzyme complexes. In this respect they resemble cytoplasmic membranes and plasma membranes derived from other tissues. Cultured lens cell contain the hydroxylating enzyme, although its activity is dependent on the culture conditions used. It is striking that in lens fibers the enzyme which seems to convert dehydroepiandrosterone specifically occurs on the plasma membranes, whereas, for instance, in liver, hemoproteins localized on the endoplasmic reticulum, exert hydroxylation activity towards a variety of steroids. This suggests some regulatory role for dehydroepiandrosterone in lens growth and metabolism.

Isolation and translation of non-crystallin messenger RNA from calf lens.

Affinith chromatography of lens polyribosomal RNA on oligo(dT)-cellulose yields three fractions. As arule the second fraction has been neglected in other studies reported in the literature. According to our investigations this fraction in particular contains the messengers for the non-crystallin lens proteins.