C.M.A.A. Goos

The use of liposomes in the topical application of steroids

The effect of topical application of the androgen 5α‐dihydrotestosterone (DHT), both encapsulated in liposomes and solved in acetone, has been evaluated using the female hamster flank organ as a model system. Systemic absorption of DHT was significant from the acetone solution, but negligible from the liposome system. The topical biological effect is, however, proportionally diminished when the liposome system is used. Under the experimental conditions used, the liposome system had no advantages over application in acetone in this model.

Evaluation of the hamster flank organ test for the screening of anti-androgens

The hamster flank organ test as routinely used is not a reliable guide to the response of sebaceous glands to androgens.

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.

Androgenic effect of testosterone and some of its metabolites in relation to their biotransformation in the skin.

Testosterone and several of its metabolites were tested in the female hamster flank organ. Microscopical examination was carried out and some histological features were quantified. Testosterone, 5α‐dihydrotestosterone and 3α‐androstanediol were very effective in stimulating the growth of the sebaceous structure, whereas 3β‐androstanediol showed no effect at all. Androsterone could evoke only a small effect. The metabolism of these steroids was studied in the hamster flank organ, hamster skin and in human scalp hair follicles and the possible interrelationship between androgenic effect and metabolism is discussed.

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.

Metabolism of benzo(a)pyrene in bovine lens epithelium.

Bovine lens epithelium contains an enzyme system that metabolizes the carcinogen benzo(a)-pyrene. The major ethylacetate-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 expoxide hydratase, prevents the formation of the dihydrodiols. The overall metabolism can be inhibited by the addition of α-naphthoflavone. The metabolism of benzo(a)pyrene in cultured lens epithelial cells has also been studied. It is found that the activity of aryl hydrocarbon hydroxylase (AHH) is strongly decrease in culture. The decline in AHH activity can be reduced by the addition of an unphysiological concentration of nicotinamide.

Determination of glycogen and enzymes of glycogen metabolism in human hair follicles

The skin epithelium and its organelles use glycogen as well as glucose as source of energy. Therefore the characterisation of glycogen metabolism and the enzymes involved is important in the study of mechanisms regulating the normal or abnormal differentiation of skin organelles such as sebaceous glands and hair follicles.The present paper describes fluorimetric methods for the determination of glycogen and for the measurements of phosphorylase and phosphorylase kinase activity in one and the same lysate of minute tissue samples. The methods were tested for their suitability on freshly isolated human hair follicles and cultured hair follicle cells. The possible use of these techniques for studies on the pathophysiology of acne and hirsutism is discussed.