Direct quantitative digital autoradiography of testosterone metabolites in the pilosebaceous unit: an environmentally advantageous trace radioactive technology

Vingler, Philippe; Filthuth, H.; Bague, Arlette; Pruche, Francis; Kermici, M.

doi:10.1016/0039-128x(93)90083-y

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…Our results are consistent with previous observations which indicate that 501-reduc tase, 17(3-HSD and 3(3-HSD are indeed active in the pilosebaceous unit [25,30], Of particu lar interest is the observation that the individ ual compartments exhibit a considerably dif ferent pattern of expression for steroidogene sis enzymes. Though it is obviously prema ture to conclude that mRNA levels will neces sarily reflect steady-state enzyme activity, nonetheless this suggests that all the compart ments will have the capacity to convert testos terone to DHT.…”

Section: Resultssupporting

confidence: 82%

“…Though it is obviously prema ture to conclude that mRNA levels will neces sarily reflect steady-state enzyme activity, nonetheless this suggests that all the compart ments will have the capacity to convert testos terone to DHT. Further, the measured levels of 5a-Rl mRNA for freshly dissected seba ceous gland (10%), primary culture of seba ceous gland (4.7%), in plucked hairs from dif ferent donors (mean = 10.3%) and different organs showed a strong correlation with pre viously reported enzyme activities [25], Im portantly, this predicts that the steroid metab olizing activity of the compartments associat ed with the PSU is at a level comparable to those found in other tissues reported to be actively involved in steroid metabolism.…”

Section: Resultsmentioning

confidence: 96%

“…Several biochemical studies have clearly shown that the PSU contains androgen recep tors [22][23][24] and is able to convert testosterone into the more active metabolite DHT [25]. As summarized in figure 1, several enzyme subtypes may be involved in this metabolic path way: (1) 17P-Hydroxysteroid dehydrogenase type 1 ortype 2 activity can convert androstenedione into testosterone and 5a-androstenedione into DHT; (2) 5a-reductasc type 1 and type 2 activities can convert testosterone into dihydrotestosterone [12][13][14][15][16][17][18]26].…”

Section: Resultsmentioning

confidence: 99%

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Messenger RNA Expression of Steroidogenesis Enzyme Subtypes in the Human Pilosebaceous Unit

Courchay

Boyera²,

Ba³

et al. 1996

Skin Pharmacol Physiol

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In order to define the respective involvement of steroidogenesis enzymes subtypes in the control of hair follicle homeostasis, we evaluated, by semiquantitative RT/PCR, the expression levels of mRNAs coding for 17 β-hydroxysteroid dehydrogenase type 1 and type 2, 3β-hydroxysteroid dehydrogenase, Cyt.P450-aromatase, steroid 5α-reductase type 1 and type 2 and 11 β-hydroxysteroid dehydrogenase. These assays were performed for several components of the pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and primary culture of dermal papilla, as well as other tissues involved in an active steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and adrenals) as controls. We found that plucked hair (i.e. mainly keratinocytes from the inner and outer root sheaths) expressed: (1) very high levels of 17β-hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and placenta; (2) high levels of steroid 5-α-reductase type 1 corresponding to levels found in testis, liver and ovary, and moderate levels of 17 β-hydroxysteroid dehydrogenase type 1, which corresponded to the expression in testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3β-hydroxysteroid dehydrogenase and steroid 5α-reductase type 2 were poorly expressed in the pilosebaceous unit as compared with other tissues. Interestingly, expression patterns of these enzymes in primary cultures of dermal papilla were distinctive since 5α-reductase type 1 and 11 β-hydroxysteroid dehydrogenase were the only mRNA detected. Taken together, these results suggest that not only sebaceous gland but also outer root sheath keratinocytes may contribute, through the activity of the steroid 5α-reductase type 1, to the pathogenesis of androgen-dependent alopecia.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Messenger RNA Expression of Steroidogenesis Enzyme Subtypes in the Human Pilosebaceous Unit

Courchay

Boyera²,

Ba³

et al. 1996

Skin Pharmacol Physiol

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“…For steroid metabolite identification two‐dimensional TLC is a valuable method ( 28). Identification of metabolites was conducted using a technique modified from a procedure described previously ( 29). After incubation, metabolites were extracted as described above.…”

Section: Methodsmentioning

confidence: 99%

Characterization of 17β‐Hydroxysteroid Dehydrogenase Activity in Brain Tissue: Testosterone Formation in the Human Temporal Lobe

Steckelbroeck

Stoffel‐Wagner

et al. 1999

J Neuroendocrinology

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Sex steroids exert important effects on the central nervous system (CNS). Although the formation of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) metabolites in the CNS was discovered almost 30 years ago, conclusive studies concerning 17beta-HSD activity in the human brain are still lacking. Therefore, we investigated 17beta-HSD in vitro activity in human temporal lobe biopsies of 13 women and 13 men using radioactively labelled androstenedione, testosterone, oestrone and 17beta-oestradiol and compared it to that in human placenta, liver, testis and prostate. We could demonstrate androgenic and oestrogenic 17beta-HSD activities in all tissues under investigation. The reduction of androstenedione and oestrone in brain was NADPH dependent with a broad pH optimum between 6.5 and 9.0, whereas the oxidation of testosterone and 17beta-oestradiol was NAD dependent with a pH optimum of >/=9.0. Using optimum cofactors sex differences of brain 17beta-HSD activities were not observed. Conversion of androstenedione, testosterone, oestrone and 17beta-oestradiol was significantly higher in the subcortical white matter than in the cerebral cortex. We could demonstrate a significant formation of testosterone in the brain tissue of all patients under investigation. Substrate specificity and cofactor requirement patterns as well as pH optima and kinetic properties suggest the occurrence of 17beta-HSD type 3 and type 4 in the human temporal lobe.

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“…Since dihydrotestosterone, a well-known negative signal for scalp hair growth, is produced in hair follicles from testosterone through the action of 5a-reductase(s) [18] and since we [ 12] and others [ 19,20] reported the presence of 5a-reductase isozymes in the human scalp pilosebaceous unit, it is likely that these en zymes and other steroidogenesis enzymes [ 12] might be, to some extent, transcriptionally upregulated by IL-la. This remains however to be established.…”

Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Cytokine Cascade in Human Plucked Hair

Mahé

Buan

Billoni

et al. 1996

Skin Pharmacol Physiol

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Using reverse transcriptase polymerase chain reaction we showed that freshly plucked human anagen hair expressed both type 1 (80 kD) and type 2 (60 kD) interleukin (IL)-1 receptor mRNAs. The IL-1 receptor type 1 was functional since after in vitro stimulation of plucked hair with IL-1Α, we observed the induction of mRNA(s) for the inflammatory cytokines IL-1Β, tumour necrosis factor Α and IL-6 as well as for the chemokines monocyte chemotactic and activating factor and IL-8. In addition, the growth of dissected human anagen hairs in culture in vitro was significantly and dose-depen-dently inhibited by IL-1Α as a consequence of hair bulb degradation. These observations, together with those of other authors in IL-1Α transgenic mice evidence the inhibitory role of IL-1 on human hair growth. Therefore, in order to identify individuals with high inflammatory potential in their hair follicle environment, we designed a rapid and simple assay to detect variations in the level of IL-1Α production in the overnight supernatant of plucked hairs in culture. We observed that 32.7% of the specimens from the volunteers tested (n = 116) could be considered highly inflammatory in terms of IL-1Α production. Altogether, these results suggest that in alopecia androgenetica, hair growth might be negatively influenced by IL-1, directly produced by the outer root sheath keratinocytes. Consequently, identifying the ‘inflammatory alopecic individual’ might be of clinical interest to discriminate among individuals for whom anti-IL-1 strategies might be of therapeutic relevance.

show abstract

Direct quantitative digital autoradiography of testosterone metabolites in the pilosebaceous unit: an environmentally advantageous trace radioactive technology

Cited by 6 publications

References 24 publications

Messenger RNA Expression of Steroidogenesis Enzyme Subtypes in the Human Pilosebaceous Unit

Messenger RNA Expression of Steroidogenesis Enzyme Subtypes in the Human Pilosebaceous Unit

Characterization of 17β‐Hydroxysteroid Dehydrogenase Activity in Brain Tissue: Testosterone Formation in the Human Temporal Lobe

Pro-Inflammatory Cytokine Cascade in Human Plucked Hair

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