Localization of 17beta-hydroxysteroid dehydrogenase and characterization of testosterone in the brain of the male frog.

Mensah‐Nyagan, Ayikoe Guy; Feuilloley, Marc; do-Rego, Jean-Claude; Marcual, Albert; Lange, Catherine; Tonon, Marie Christine; Pelletier, Georges; Vaudry, Hubert

doi:10.1073/pnas.93.4.1423

Cited by 110 publications

(62 citation statements)

References 26 publications

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“…Previously, the presence of type 1 17 -HSD primarily catalyzing the interconversion of E1 and E2 with a predominance of the reductive pathway was demonstrated in the rat, frog and human fetal brain using immunocytochemical techniques (Milewich et al 1990, Pelletier et al 1995, Mensah-Nyagan et al 1996. We found that also in the human temporal lobe 17 -HSD type 1 is expressed with mRNA concentrations about 10 000-fold lower than in the placenta.…”

Section: Discussionmentioning

confidence: 90%

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe

Stoffel‐Wagner¹,

Watzka²,

Steckelbroeck³

et al. 1999

Journal of Endocrinology

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Sex steroid hormones exert important biological effects on the brain. Moreover, an extensive sex steroid metabolism occurs in the brain. In sex steroid metabolism 17 -hydroxysteroid dehydrogenases (17 -HSDs) play essential roles in catalyzing the final steps in androgen and estrogen biosynthesis. Recently four types of human 17 -HSDs and a pseudogene of the type 1 isoform were identified. To date, 17 -HSD has not been extensively studied in the human brain. Therefore, we investigated the mRNA expression of the four isozymes of 17 -HSD as well as the pseudogene of the type 1 isoform in the human temporal lobe to determine the predominant isoforms and, moreover, to elucidate the existence of possible sex and age differences. We studied biopsy materials from the temporal lobe of 34 women, 32 men and 10 children. Quantification of different mRNAs was achieved by competitive reverse transcription-PCR. 17 -HSD 1, 17 -HSD 3 and 17 -HSD 4 were expressed in the human temporal lobe of children and adults, whereas 17 -HSD 2 and the pseudogene of 17 -HSD 1 were not expressed. In adults, 17 -HSD 3 and 17 -HSD 4 mRNA concentrations were significantly higher in the subcortical white matter (17 -HSD 3: 14 591 3457 arbitrary units (aU), mean ...; 17 -HSD 4: 1201 212 aU) than in the cortex (17 -HSD 3: 5428 1057 aU, P<0·0002; 17 -HSD 4: 675 74 aU, P<0·004). 17 -HSD 1 concentrations did not differ significantly between the white matter (3860 1628 aU) and the cortex (2525 398 aU) of adults. In conclusion, the present study demonstrates the expression of 17 -HSD 1, 3 and 4 mRNAs in the human temporal lobe. Together with CYP19 AROM and 5 -reductase, known to be expressed in the human brain, the expression of 17 -HSD 1, 3 and 4 mRNAs indicates the major importance of local steroid biosynthesis in the brain.

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Section: Discussionmentioning

confidence: 90%

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe

Stoffel‐Wagner¹,

Watzka²,

Steckelbroeck³

et al. 1999

Journal of Endocrinology

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“…However, recent studies indicate that non-gonadal tissues can produce sex steroids and sex-steroid precursors (Labrie et al 1995;Mensah-Nyagan et al 1996;Baulieu 1998;Schlinger et al 1999), and these non-gonadal steroids could support winter territoriality. The adrenals can secrete androgen precursors in several species, perhaps including birds (Schlinger et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Oestrogen regulates male aggression in the non–breeding season

Soma

Tramontin

Wingfield

2000

Proc. R. Soc. Lond. B

192

112

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Extensive research has focused on territorial aggression during the breeding season and the roles of circulating testosterone (T) and its conversion to 17b -oestradiol (E 2 ) in the brain. However, many species also defend territories in the non-breeding season, when circulating T-levels are low. The endocrine control of non-breeding territoriality is poorly understood. The male song sparrow of Washington State is highly territorial year-round, but plasma T is basal in the non-breeding season (autumn and winter). Castration has no e¡ect on aggression in autumn, suggesting that autumnal territoriality is independent of gonadal hormones. However, non-gonadal sex steroids may regulate winter territoriality (e.g. oestrogen synthesis by brain aromatase). In this ¢eld experiment, we treated wild non-breeding male song sparrows with a speci¢c aromatase inhibitor (fadrozole, FAD) using micro-osmotic pumps. FAD greatly reduced several aggressive behaviours. The e¡ects of FAD were reversed by E 2 replacement. Treatment did not a¡ect body condition or plasma corticosterone, suggesting that all subjects were healthy. These data indicate that E 2 regulates male aggression in the non-breeding season and challenge the common belief that aggression in the non-breeding season is independent of sex steroids. More generally, these results raise fundamental questions about how sexual and/or aggressive behaviours are maintained in a variety of model vertebrate species despite low circulating levels of sex steroids or despite castration. Such nonclassical endocrine mechanisms may be common among vertebrates and play an important role in the regulation of behaviour.

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“…Other enzymes, such as 3␤-hydroxysteroid dehydrogenase͞⌬ 5 -⌬ 4 -isomerase (3␤-HSD) and 17␤-HSD, also are expressed in the amphibian brain and are involved in the conversion of pregnenolone to progesterone, androstenedione, and testosterone (8,10,11).…”

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confidence: 99%

7α-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system

Morikura

Ukena

Baulieu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

192

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It is becoming clear that steroids can be synthesized de novo by the brain and other nervous systems. Such steroids are called neurosteroids, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. In this study, we show that the newt brain actively produces 7␣-hydroxypregnenolone, a previously undescribed amphibian neurosteroid that stimulates locomotor activity. 7␣-hydroxypregnenolone was identified as a most abundant amphibian neurosteroid in the newt brain by using biochemical techniques combined with HPLC, TLC, and GC-MS analyses. The production of 7␣-hydroxypregnenolone in the diencephalon and rhombencephalon was higher than that in the telencephalon and peripheral steroidogenic glands. In addition, 7␣-hydroxypregnenolone synthesis in the brain showed marked changes during the annual breeding cycle, with a maximal level in the spring breeding period when locomotor activity of the newt increases. Behavioral analysis of newts in the nonbreeding period demonstrated that administration of this previously undescribed amphibian neurosteroid acutely increased locomotor activity. In vitro analysis further revealed that 7␣-hydroxypregnenolone treatment resulted in a dose-dependent increase in the release of dopamine from cultured brain tissue of nonbreeding newts. The effect of this neurosteroid on locomotion also was abolished by dopamine D 2-like receptor antagonists. These results indicate that 7␣-hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts through the dopaminergic system. This study demonstrates a physiological function of 7␣-hydroxypregnenolone that has not been described previously in any vertebrate class. This study also provides findings on the regulatory mechanism of locomotor activity from a unique standpoint.neurosteroids ͉ dopamine release ͉ newt brain ͉ seasonal changes

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Localization of 17beta-hydroxysteroid dehydrogenase and characterization of testosterone in the brain of the male frog.

Cited by 110 publications

References 26 publications

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe

Oestrogen regulates male aggression in the non–breeding season

7α-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system

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