El ángulo papila-fóvea y la torsión ocular compensatoria, clave en su interpretación / Disc-foveal angle and ocular counterrolling as a key in its interpretation

OBJETIVO: Describir una técnica rápida para medir el ángulo papila-fóvea (APF), determinar sus valores normales y su relevancia a la hora de analizar retinografías apareadas. MÉTODOS: En 20 sujetos se realizaron 440 retinografías (3 D OCT-2000, Topcon Corporation, Tokio, Japón) en 11 posiciones diferentes de la cabeza (cervical range of motion [CROM], Performance Attainment Associates). Se analizó el APF mediante el programa Keynote v.6.2.2 y se estudió la reproducibilidad y correlación entre los retinógrafos 3 D OCT-2000 y TRC-50EX (Topcon Corporation, Tokio, Japón). RESULTADOS: La media del APF en el ojo derecho (OD) y en el ojo izquierdo (OI) fue de 5,5 ± 3,4° y de 8,6 ± 2,9°, con una diferencia de 3,1° (p = 0,001 test del signo-rango de Wilcoxon). La media de la diferencia absoluta del APF entre ambos ojos fue de 3,5 ± 2,6°; aumentando con la inclinación cefálica en el plano frontal (p = 0,000 test del signo-rango de Wilcoxon). La media de la suma del APF de ambos ojos fue de 14,1 ± 5,4°. La media de la torsión ocular compensatoria (TOC) con la cabeza inclinada 20 y 40° a la derecha fue de 7,1 y 12,2° en el OD y de 7,7 y 12,1° en el OI. Con la cabeza inclinada 20 y 40° a la izquierda, la media fue de 4,4 y 8° en el OD y de 4,2 y 8,7° en el OI (p = 0,000 test del signo-rango de Wilcoxon). Los retinógrafos mostraron alta correlación y reproducibilidad. CONCLUSIÓN: Nuestra técnica es rápida y reproducible. El OI muestra mayor APF que el OD. La TOC solo ocurre en el plano frontal. Estos aspectos son relevantes al analizar retinografías apareadas

PURPOSE: Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs. METHODS: DFA was analysed using the software program Keynote v.6.2.2 on 440 fundus photographs (3 D OCT 2000, Topcon Corporation, Tokio, Japan) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3 D-2000 and TRC-50EX, Topcon Corporation, Tokio, Japan) was performed. RESULTS: Mean DFA of the right and left eye was 5.5 ± 3.4° and 8.6 ± 2.9°, with a difference of 3.1° (P = 0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5 ± 2.6°; an increase was seen with increasing head tilt (p = 0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1 ± 5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in the right eye and 7.7° and 12.1° in the left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in the right eye and 4.2° and 8.7° in the left eye (P = 0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility. CONCLUSIONS: Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher DFA than right eye. OCR occurs only in the roll plane. This information is of value when analyzing paired fundus photographs

Disc-foveal angle and ocular counterrolling as a key in its interpretation. / El ángulo papila-fóvea y la torsión ocular compensatoria, clave en su interpretación.

PURPOSE: Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs. METHODS: DFA was analysed using the software program Keynote v.6.2.2 on 440 fundus photographs (3D OCT 2000, Topcon Corporation, Tokio, Japan) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3D-2000 and TRC-50EX, Topcon Corporation, Tokio, Japan) was performed. RESULTS: Mean DFA of the right and left eye was 5.5±3.4° and 8.6±2.9°, with a difference of 3.1° (P=0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5±2.6°; an increase was seen with increasing head tilt (P=0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1±5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in the right eye and 7.7° and 12.1° in the left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in the right eye and 4.2° and 8.7° in the left eye (P=0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility. CONCLUSIONS: Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher DFA than right eye. OCR occurs only in the roll plane. This information is of value when analyzing paired fundus photographs.

Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages.

Brucella spp. can establish themselves and cause disease in humans and animals. The mechanisms by which Brucella spp. evade the antibacterial defenses of their host, however, remain largely unknown. We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-alpha) production upon human macrophage infection. This inhibition is associated with a nonidentified protein that is released into culture medium. Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production. Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis) on TNF-alpha production. For this purpose, omp25 and omp31 null mutants of B. suis (Deltaomp25 B. suis and Deltaomp31 B. suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-alpha. We showed that, in contrast to WT B. suis or Deltaomp31 B. suis, Deltaomp25 B. suis induced TNF-alpha production when phagocytosed by human macrophages. The complementation of Deltaomp25 B. suis with WT omp25 (Deltaomp25-omp25 B. suis mutant) significantly reversed this effect: Deltaomp25-omp25 B. suis-infected macrophages secreted significantly less TNF-alpha than did macrophages infected with the Deltaomp25 B. suis mutant. Furthermore, pretreatment of WT B. suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-alpha production during macrophage infection. These observations demonstrated that Omp25 of B. suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages.

A beneficial aspect of a CB1 cannabinoid receptor antagonist: SR141716A is a potent inhibitor of macrophage infection by the intracellular pathogen Brucella suis.

The psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC) suppresses different functions of immunocytes, including the antimicrobicidal activity of macrophages. The triggering of cannabinoid receptors of CB1 and CB2 subtypes present on leukocytes may account for these effects. We investigated the influence of specific CB1 or CB2 receptor antagonists (SR141716A and SR144528, respectively) and nonselective CB1/CB2 cannabinoid receptor agonists (CP55,940 or WIN 55212-2) on macrophage infection by Brucella suis, an intracellular gram-negative bacteria. None of the compounds tested affected bacterial phagocytosis. By contrast, the intracellular multiplication of Brucella was dose-dependently inhibited in cells treated with 10-500 nM SR141716A and 1 microM SR141716A-induced cells exerted a potent microbicidal effect against the bacteria. SR144528, CP55,940, or WIN 55212-2 did not affect (or slightly potentiated) the growth of phagocytized bacteria. However, CP55,940 or WIN 55212-2 reversed the SR141716A-mediated effect, which strongly suggested an involvement of macrophage CB1 receptors in the phenomenon. SR141716A was able to pre-activate macrophages and to trigger an activation signal that inhibited Brucella development. The participation of endogenous cannabinoid ligand(s) in Brucella infection was discussed. Finally, our data show that SR141716A up-regulates the antimicrobial properties of macrophages in vitro and might be a pharmaceutical compound useful for counteracting the development of intramacrophagic gram-negative bacteria.

In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells.

During the complex interaction between an infectious agent and a host organism, the pathogen can interfere with the host cell's programmed death to its own benefit. Induction or prevention of host cell apoptosis appears to be a critical step for determining the infection outcome. Members of the gram-negative bacterial genus Brucella are intracellular pathogens which preferentially invade monocytic cells and develop within these cells. We investigated the effect of Brucella suis infection on apoptosis of human monocytic phagocytes. The present study provides evidence that Brucella infection inhibited spontaneously occurring apoptosis in human monocytes. Prevention of monocyte apoptosis was not mediated by Brucella lipopolysaccharide and required bacterial survival within infected cells. Both invaded and noninvaded cells were protected, indicating that soluble mediators released during infection were involved in the phenomenon. Analysis of Brucella-infected monocytes revealed specific overexpression of the A1 gene, a member of the bcl-2 family implicated in the survival of hematopoietic cells. Brucella infection also rendered macrophage-like cells resistant to Fas ligand- or gamma interferon-induced apoptosis, suggesting that Brucella infection protected host cells from several cytotoxic processes occurring at different steps of the immune response. The present data clearly show that Brucella suis modulated the monocyte/macrophage's apoptotic response to the advantage of the pathogen, thus preventing host cell elimination. This might represent a strategy for Brucella development in infected hosts.

Expression and bactericidal activity of nitric oxide synthase in Brucella suis-infected murine macrophages.

We examined the expression and activity of inducible nitric oxide synthase (iNOS) in both gamma interferon (IFN-gamma)-treated and untreated murine macrophages infected with the gram-negative bacterium Brucella suis. The bacteria were opsonized with a mouse serum containing specific antibrucella antibodies (ops-Brucella) or with a control nonimmune serum (c-Brucella). The involvement of the produced NO in the killing of intracellular B. suis was evaluated. B. suis survived and replicated within J774A.1 cells. Opsonization with specific antibodies increased the number of phagocytized bacteria but lowered their intramacrophage development. IFN-gamma enhanced the antibrucella activity of phagocytes, with this effect being greater in ops-Brucella infection. Expression of iNOS, interleukin-6, and tumor necrosis factor alpha (TNF-alpha) mRNAs was induced in both c-Brucella- and ops-Brucella-infected cells and was strongly potentiated by IFN-gamma. In contrast to that of cytokine mRNAs, iNOS mRNA expression was independent of opsonization. Similar levels of iNOS mRNAs were expressed in IFN-gamma-treated cells infected with c-Brucella or ops-Brucella; however, expression of iNOS protein and production of NO were detected only in IFN-gamma-treated cells infected with ops-Brucella. These discrepancies between iNOS mRNA and protein levels were not due to differences in TNF-alpha production. The iNOS inhibitor N omega-nitro-L-arginine methyl ester increased B. suis multiplication specifically in IFN-gamma-treated cells infected with ops-Brucella, demonstrating a microbicidal effect of the NO produced. This observation was in agreement with in vitro experiments showing that B. suis was sensitive to NO killing. Together our data indicate that in B. suis-infected murine macrophages, the posttranscriptional regulation of iNOS necessitates an additive signal triggered by macrophage Fcgamma receptors. They also support the possibility that in mice, NO favors the elimination of Brucella, providing that IFN-gamma and antibrucella antibodies are present, i.e., following expression of acquired immunity.

mRNAs encoding CCKB but not CCKA receptors are expressed in human T lymphocytes and Jurkat lymphoblastoid cells.

We previously reported the existence of pharmacologically related gastrin/CCKB type receptors (CCKB-R) in a variant of Jurkat T lymphoblastoid cells (JK(CD3- CD4+)). We studied here the expression of mRNAs encoding CCKA and CCKB receptors in various human white cells by means of Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Using CCKB-R specific primers, we detected a significant expression of CCKB-R mRNA in JK(CD3- CD4+) cells. These transcripts were also expressed, at a lower level, in two other Jurkat clones (JK(CD3+ CD4-) and JK(CD3+ CD4+)), in peripheral blood lymphocytes (PBL) and in purified CD4+ and CD8+ lymphocytes. Activation of Jurkat cells and PBL by T cells mitogenic lectins (jacalin, phytohemaglutinin) did not modify CCKB-R mRNA expression. In all these cells, using CCKA-R specific primers, we could not amplify any specific cDNA fragment corresponding to this receptor. Neither CCKB-R nor CCKA-R mRNAs could be detected in monocytic cells. Our data show for the first time a constitutive expression of CCKB-R transcripts in lymphoid cells. Moreover, the modulation of immunocyte functions by cholecystokinin-related peptides could occur through CCKB-R rather than CCKA-R and affect lymphocytes rather than monocytes.

Ophthalmoscopic evolution of papillary colobomatous malformations.

We describe congenital colobomatous malformations of the optic nerve and the clinical variations and complications that may appear eventually in them. We also present two clinical cases of patients with papillary colobomatous defects where spontaneous variations have been observed throughout their evolution and where the current ophthalmoscopic aspect is completely different from the initial one. Finally, bearing in mind the embryologic origin and histologic structure of these anomalies, we develop a hypothesis that explains the physiopathologic mechanism that causes the clinical changes described in each case.

Molecular biology of disorders of sex differentiation.

Sexual ambiguity can be a difficult and sometimes confusing diagnostic problem in children. Recent developments in molecular biology have provided the opportunity to analyze the gene responsible for testicular determination, SRY, the androgen receptor gene and the gene encoding the cP450 enzyme specific for 21-hydroxylation, CYP21B, whose defects are responsible for congenital adrenal hyperplasia. Southern-blotting studies and PCR analyses of SRY, androgen receptor and CYP21B genes can be routinely used for the direct diagnosis of gonadal dysgenesis, androgen insensitivity syndromes and congenital adrenal hyperplasia, respectively. In sex-reversed XY females, several de novo mutations or deletions in the SRY gene have been reported. Defects in the human androgen receptor cause a spectrum of defects in male phenotypic sexual development associated with abnormalities in the receptor protein. Analyses of the androgen receptor gene structure have identified the causative mutation in some families: mutations that result in large-scale alterations of the structure of the androgen receptor, mRNA or gene mutations that alter the primary structure of the androgen receptor protein and mutations that alter the level of mRNA. The diversity of clinical phenotypes, apparent in 21-hydroxylase deficiency, is paralleled by a considerable degree of mutational heterogeneity in the CYP21 gene locus. Various changes causing severe 21-hydroxylase deficiency have been reported: point mutations, gene conversions and gene deletions. In conclusion, substantial progress has been made elucidating genetic defects causing sex reversal in XY females, the androgen insensitivity syndrome and congenital adrenal hyperplasia. Molecular genetics can also be applied for carrier identification and prenatal diagnosis.

Association of the Hind III polymorphism with the androgen receptor gene in partial androgen insensitivity syndrome.

Partial androgen insensitivity syndrome (PAIS) is an X-linked disorder resulting from defects in the intracellular androgen receptor (AR). The cloning of the AR cDNA has provided the molecular tools to identify gene abnormalities. Gene deletions being the exception in PAIS, prenatal diagnosis of PAIS resulting from a single base mutation in high risk families is not practical unless the mutation is already known. Brown et al. (1989) reported that 10% of normal X chromosomes present a Hind III 6.7/3.5 kb polymorphism. In this study, we report the association of the Hind II polymorphism in a woman whose son has a PAIS associated with a very low androgen receptor concentration: we differentiated the two maternal X chromosomes and characterized the affected allele. These data demonstrate that the presence of Hind III polymorphic fragments could be used in prenatal diagnosis of androgen insensitivity syndrome in high risk families.

[Physiopathology of androgen insensitivity syndromes. Contribution of molecular biology]. / Physiopathologie des syndromes d'insensibilité aux androgènes. Apport de la biologie moléculaire.

Molecular genetic study of androgen insensitivity syndrome is now easier by the development of powerful molecular tools. Complementary DNA of the androgen receptor gene has been recently cloned and sequenced. The development of cDNA probes gave the opportunity to study DNA restriction fragment length polymorphisms of patients with complete or partial androgen insensitivity syndrome. These studies demonstrated that deletions are rarely observed. Using PCR and sequencing of exons, several groups described point mutations within the androgen receptor gene. Enzymatic amplification along with denaturing gradient gel electrophoresis and single strand conformational polymorphism study allowed the description of new mutations. These powerful tools together with mRNA study, expression of muted gene, anti-receptor study had also permitted to analyze correlations between structure-function activity of the androgen receptor gene in patients with androgen insensitivity syndrome.

[Collagen and steroid hormones]. / Collagène et hormones stéroïdes.

The authors analyse the effects of steroid hormones on collagen, from up to date datas previously published and personal works. Glucocorticoids have catabolic effects; their molecular effects are reviewed. Conversely, oestrogens and androgens have an anabolic effect.

[Male pseudohermaphroditism caused by partial insensitivity to androgens. Clinical and biochemical heterogeneity]. / Pseudo-hermaphrodisme masculin par insensibilité partielle aux androgènes. Hétérogénéité clinique et biochimique.

Male pseudohermaphroditism due to partial androgen insensitivity (PAI) may be suspected clinically in case of incomplete masculinization of external genitalia in spite of age related plasma androgen levels. In 25 children or adolescents in whom PAI was suspected, the 5 alpha-reductase activity of external genitalia fibroblasts, the number of androgen receptor sites (Bmax) and the affinity of receptors for dihydrotestosterone (Kd) were studied. Clinical expression of PAI is highly polymorphic (Prader's type I to type IV), when most children (18/25) were considered as males. In a single patient the very low 5 alpha-reductase activity permitted the diagnosis of 5 alpha-reductase deficiency. The number of receptor sites (fmoles/mg DNA) varied from 0 to 730. Mean Bmax of patients (282 +/- 187 fmoles/mg DNA) was statistically lower than that of normal subjects (642 +/- 220 fmoles/mg DNA), p less than 0.05. The 5 cases in whom receptor concentrations were normal may be related to a qualitative abnormality of the androgen receptor or to a "post-receptor" defect. On the contrary no significant differences in Kd values were found. Correlation between sexual ambiguity and the number of measured receptors was not possible. These results emphasize the clinical and biochemical heterogeneity of PAI. Nevertheless, the decrease in number of androgen receptor sites remains the major data for the biochemical diagnosis of PAI. Study of post-receptor "markers" (3 alpha-reductase activity, aromatase, collagen) might allow better analysis of cases with PAI in whom androgen receptor concentrations are normal.

Specific 5 alpha-dihydrotestosterone receptor and 5 alpha-reductase activity in human amniotic fluid cells.

A macromolecular component which specifically binds tritium-labeled-dihydrotestosterone is present in cultured amniotic fluid cells. The androgen-binding complex is characterized by a 3.6S sedimentation coefficient, an apparent dissociation constant of 1 nmol/L, a mean binding capacity of 243 +/- 140 fmol/mg of DNA, and a specificity for testosterone and dihydrotestosterone. Similar properties have been reported for the androgen receptor of the fetal genital skin fibroblast, which suggests that the tritium-labeled-dihydrotestosterone-binding component in amniotic fluid cells is the androgen receptor. Amniotic fluid cell monolayers incubated with serum-free medium containing testosterone are able to transform testosterone into dihydrotestosterone. The 5 alpha-reduced product has been characterized by thin-layer chromatography and capillary column gas-liquid chromatography. Androgen receptors and 5 alpha-reductase activity are expressed in amniotic fluid cells. The prenatal diagnosis of 5 alpha-reductase deficiency or complete androgen insensitivity syndrome (testicular feminization) is thus theoretically possible and obviously prenatal testing would be indicated in the family at high risk.

Inhibition of androgen metabolism and binding by a liposterolic extract of "Serenoa repens B" in human foreskin fibroblasts.

We previously suggested [Steroids 33, (1979) 3; Steroids 37, (1981) 6] that cultured genital skin fibroblasts should prove useful for screening of potential antiandrogens in human and living target cells. "Serenoa repens" lipidic extract (S.R.E.) was recently reported (Br. J. Pharmacol., in press) to inhibit androgen action in animals. The present investigation was designed to study the antiandrogenicity of this compound in human cells: we therefore analyzed the effects of S.R.E. on the intracellular conversion of testosterone (T) to 5 alpha-reduced derivatives, and we investigated interaction of S.R.E. with the intracellular androgen-receptor complex. Since the chemical structure of the active component of S.R.E. is still unknown, results are expressed in U/ml (one unit is defined as the amount of S.R.E. required to inhibit 50% of the specific binding (IC50) of [3H]1881 to rat prostate cytosol). S.R.E. at different dilutions (5.7 to 28.6 U/ml) is added to culture media containing [3H]T or [3H]dihydrotestosterone (DHT) and incubated at 37 degrees C with cultured fibroblasts. 28.6 U/ml S.R.E. significantly alters the formation of DHT and strongly inhibits 3 ketosteroid reductase mediated conversion of DHT to 5 alpha-androstane-3 alpha, 17 beta-diol, characterized radiochemically by thin-layer chromatography. S.R.E. is a good competitor for the whole cell androgen receptor: 7.1 U/ml S.R.E. gives 50% inhibition of the binding of 2 X 10(-9) M [3H]DHT to its receptor. Competitive binding assays after cell fractionation indicate that S.R.E. is less potent in nuclear than in cytosol receptors. Sucrose gradient centrifugation of the radioactive cell lysate of fibroblasts demonstrates that 28.6 U/ml S.R.E. abolishes 70% of the 3.6 S receptor-complex radioactive peak. The present studies show that S.R.E. inhibits 5 alpha-reductase, 3-ketosteroid reductase and receptor binding of androgens in cultured human foreskin fibroblasts. As the search for the ideal antiandrogen continues, S.R.E. appears to be a new type of antiandrogenic compound as therapeutics for the treatment of benign prostatic hypertrophy, hirsutism and so forth.

[Metabolism of dihydrotestosterone in cultured skin fibroblasts: reduction to 5 alpha-androstane-3 alpha, 17 beta-diol]. / Métabolisme de la dihydrotestostérone dans le fibroblaste cutané en culture: réduction en 5 alpha-androstane 3 alpha, 17 beta diol.

Reduction of dihydrotestosterone into 5 alpha-androstan-3 alpha, 17 beta diol by 3 alpha hydroxysteroid dehydrogenase was studied in human cultured skin fibroblasts. Characterization of the 3 alpha diol was performed by gas-liquid chromatography coupled with mass spectrometry. Sex skin fibroblasts enzyme has the same Km (9.10 X 10(-6) M) as that of non sex skin fibroblasts (8.75 X 10(-6) M). On the other hand, reduction of DHT is 3 times higher in sex skin fibroblasts (Vmax = 223.9) than in non sex skin fibroblasts (Vmax = 87.9). Thus, human culturel fibroblasts appear again to be an useful tool for the study of a key-enzyme of androgen metabolism in target cells.

Androgen receptors in cultured human skin fibroblasts.

Human skin may be considered as a target organ for androgens, since events characteristic of androgen action have been described in this tissue, as well as in cultured human skin fibroblasts. The culture of human skin fibroblasts gives the opportunity to work on living cells, under controlled conditions, in a renewable material from a single skin biopsy. Using this method, we showed the presence od DHT-receptors in the human fetus and we studied the ontogenesis of androgen receptors in relation to sexual differentiation. In the neonatal period, the physiological T rise was not concurrent with a variation in sex skin androgen receptors. The evolution of DHT binding during puberty is now under investigation. These data suggest that the androgen receptor is not modulated by plasma androgens. Androgen receptor determination is of value in defining the biochemical defects involved in partial and complete androgen insensitivity syndrome (twenty-six cases in our study). In idiopathic hirsutism, DHT binding is used to detect an eventual local hypersensitivity. Fibroblast cultures have also been shown to be an excellent model for the screening of compounds which might block the expression of androgen action by competing for the androgen receptors. Cultured skin fibroblasts are a valuable model for the study of androgen and antiandrogen action in human skin.

[Effect of cyproterone acetate on the 3 alpha-hydroxysteroid-dehydrogenase activity of cutaneous fibroblasts in culture]. / Action de l'acétate de cyprotérone sur l'activité 3 alpha-hydroxystéroïde déshydrogénase du fibroblaste cutané en culture.

In men, parallel variations in urinary 3 alpha 5 alpha androstane 17 beta diol with the amount of sex skin fibroblast DHT receptors rise the question of a relationship of 3 ketosteroid reductase activity and specific DHT binding. To test this hypothesis, we measured 3 alpha 5 alpha androstane 17 beta diol biosynthesis in cultured sex skin fibroblasts, in the presence of high amounts of cyproterone acetate which competes with DHT for its receptor: when 95% of DHT is displaced by cyproterone acetate, the 3 keto steroid reductase activity remains unchanged. These results suggest that the relationship of 3-keto-steroid reductase activity and androgen receptors is unlikely.