Activity and expression of steroidogenic enzymes in the brain of adult zebrafish

Abstract

The brain of adult teleost fish exhibits several unique and interesting features, notably an intense neurogenic activity linked to persistence of radial glial cells acting as neural progenitors, and a high aromatase activity supported by strong expression of the cyp19a1b gene. Strikingly, cyp19a1b expression is restricted to radial glial cells, suggesting that estrogens are able to modulate their activity. This raises the question of the origin, central or peripheral, of C19 androgens available for aromatization. This study aimed to investigate the activity and expression of other main steroidogenic enzymes in the brain of adult zebrafish. We demonstrate by high-performance liquid chromatography that the zebrafish brain has the ability to convert [³H]-pregnenolone into a variety of radiolabeled steroids such as 17OH-pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydro-testosterone, estrone, estradiol, progesterone, and dihydro- and tetrahydro-progesterone. Next, we show by in situ hybridization that messengers for key steroidogenic enzymes, such as Cyp11a1 (P450(SCC)), 3β-Hsd, Cyp17 and Cyp19a1b, are widely expressed in the forebrain where they exhibit an overall similar pattern. By combining aromatase B immunohistochemistry with in situ hybridization, we show that cyp11a1, 3β-hsd and cyp17 messengers are found in part in aromatase B-positive radial processes, suggesting mRNA export. This set of results provides the first demonstration that the brain of fish can produce true neurosteroids, possibly in radial glial cells. Given that radial glial cells are brain stem cells during the entire lifespan of fish, it is suggested that at least some of these neurosteroids are implicated in the persisting neurogenic process.

11β-Hydroxysteroid dehydrogenase type 2 in zebrafish brain: a functional role in hypothalamus-pituitary-interrenal axis regulation

“…This suggests that the developmental loss of brain Hsd11b2 observed in higher vertebrates may not occur in fish, while the functional relevance of this observation from an evolutionary standpoint awaits further study. Interestingly, the pattern of hsd11b2 expression in the brain reported in this study parallels the distribution of key steroidogenic enzymes in the adult zebrafish brain (Diotel et al 2010(Diotel et al , 2011, including prominent expression in the telencephalon (Fig. 3A) and peripheral edges of the brain (Fig.…”

Steroid modulation of neurogenesis: Focus on radial glial cells in zebrafish

“…Our laboratory recently demonstrated that the brain of adult zebrafish was able to de novo synthesize a wide variety of radiolabeled neurosteroids from [ 3 H]-pregnenolone. Among these locally-produced steroids, there are notably dehydroepiandrosterone (DHEA), androgens (i.e., testosterone), estrogens (i.e., estrone and 17b estradiol), progesterone and derivatives [51,55]. Such results clearly evidence that 17b-hsd, 3a and 3b-hsd, cyp17, 5a-reductase and cyp19a1b (AroB) are expressed and biologically active in the brain of adult zebrafish.…”

“…While neurosteroids synthesis is widely documented in mammals, only few studies focused on de novo steroid synthesis in the brain of teleost fish [51][52][53][54][55] Such a feature raises the question of the origin, local and/or peripheral, of C19 androgens available for brain aromatization. Our laboratory recently demonstrated that the brain of adult zebrafish was able to de novo synthesize a wide variety of radiolabeled neurosteroids from [ 3 H]-pregnenolone.…”

Biosynthesis and Biological Actions of Pineal Neurosteroids in Domestic Birds

“…However, studies conducted over the past two decades have demonstrated that the central and peripheral nervous systems have the capacity of synthesizing steroids, the so-called ‘neurosteroids' [for reviews, see [1,2,3,4,5,6,7,8,9]. De novo formation of neurosteroids in the brain was originally demonstrated in mammals [10,11,12,13,14,15,16,17,18], and subsequently in birds [2,6,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], amphibians [36,37,38,39,40,41,42,43,44,45,46,47] and fish [48,49,50,51]. Therefore, de novo synthesis of neurosteroids from cholesterol in the brain appears to be conserved across the subphylum vertebrata [1,2,3,4,5,6,7,8,9].…”