Region-Specific Regulation of Cytochrome P450 Aromatase Messenger Ribonucleic Acid by Androgen in Brains of Male Rhesus Monkeys1

Resko, John A.; Pereyra-Martinez, Ada C.; Stadelman, Henry L.; Roselli, Charles E.

doi:10.1095/biolreprod62.6.1818

Cited by 36 publications

(25 citation statements)

References 32 publications

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“…Similar observations dealing with the regulation of aromatase activity by androgens have been reported in the brain of the rat (Roselli & Resko 1984, Zwain et al 1997, Resko et al 2000. Below a threshold of 100 ng/ml testosterone the Leydig cell increase of estradiol output is the consequence of either post-transcriptional events and/or use of available mRNAs without transcriptional effects (which may indeed explain the slight diminution of the amount of P450arom mRNA; Fig.…”

Section: Discussionsupporting

confidence: 77%

Regulation of cytochrome P450 aromatase gene expression in adult rat Leydig cells: comparison with estradiol production

Genissel¹,

Levallet²,

Carreau³

2001

Journal of Endocrinology

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Regulation of aromatase gene expression in purified rat Leydig cells has not yet been investigated. Therefore, using a highly specific quantitative RT-PCR method, we have measured the amount of cytochrome P450 aromatase (P450arom) mRNA and aromatase activity in mature rat Leydig cells submitted to various treatments during 24 h. Estradiol production was enhanced in a dose-related manner in the presence of testosterone, the maximum (28% increase) being obtained with 200 ng/ml. Related to the P450arom mRNA levels, a decrease was observed in the presence of low concentrations (50 and 100 ng/ml) of testosterone, then a 20% increase of the amount of transcripts was recorded for the higher concentrations (200-500 ng/ml). The same result was obtained in the presence of 5 -dihydrotestosterone (an androgen resistant to aromatase activity). The addition of ovine LH (oLH; 0·1-50 ng/ml) to the Leydig cell culture medium induced a dose-related augmentation of estradiol output up to 10 ng/ml oLH, although a decrease was observed with 50 ng/ml when compared with maximal values. mRNA levels slightly decreased in the presence of low concentrations (0·1-1 ng/ml) of oLH, an effect that was abolished by the addition of testosterone; mRNA levels were increased by oLH (5-10 ng/ml) 35 and 75% respectively in the absence and presence of testosterone (when compared with Leydig cells incubated without treatment). With 50 ng/ml oLH, a large augmentation (twofold) of the P450arom mRNA level either without or with testosterone was observed. Dibutyryl cyclic AMP (1 mM) mimicked the effect of oLH. The half-life of the P450arom mRNAs was twofold increased in the presence of testosterone and oLH when compared with the half-life in the absence of treatment (5·8 0·6 h). Taken together, our data have demonstrated that, in freshly isolated Leydig cells from mature rat testes, the regulation of aromatase expression and enzymatic activity is under LH (through cyclic AMP) and steroid control; moreover seminiferous tubule-secreted factor(s) are also involved. Therefore, rat Leydig cell aromatase is controlled at both transcriptional and post-transcriptional steps by endocrine and/or locally produced modulators.

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Section: Discussionsupporting

confidence: 77%

Regulation of cytochrome P450 aromatase gene expression in adult rat Leydig cells: comparison with estradiol production

Genissel¹,

Levallet²,

Carreau³

2001

Journal of Endocrinology

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“…Data have been reported showing a positive role for androgens in aromatase expression in rat testicular somatic cells; these studies were in the presence of a saturating amount of testosterone (200 ng/ml) (Levallet & Carreau 1997, Genissel & Carreau 2001. Moreover in the rat brain (Roselli & Resko 1984) as well as in the brain of male rhesus monkeys (Resko et al 2000) androgens regulate aromatase at both the transcriptional level and the enzyme activity via the presence of ARs (Roselli et al 2001). In male gonad the localization of AR is a subject of controversy (for review see Eddy 2002); some reports have demonstrated the presence of immunoreactive AR in germ cells (Vornberger et al 1994, Zhou et al 1996 and other studies have shown that only testicular somatic cells express AR (Suarez-Quian et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Steroids control the aromatase gene expression in purified germ cells from the adult male rat

Bourguiba¹,

Lambard²,

Carreau³

2003

Journal of Molecular Endocrinology

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The ability of the testis to convert irreversibly androgens into estrogens is related to the presence of a microsomal enzymatic complex named aromatase. In rodents, germ cell production of estrogens is known, although the regulation of the cytochrome P450 aromatase (P450 arom) gene expression is not completely elucidated. In the present study, we have investigated the putative effects of steroids (testosterone, 5α-dihydrotestosterone (DHT) and estradiol) on Cyp19 gene expression in purified adult rat pachytene spermatocytes (PSs) and round spermatids (RSs). Using a highly specific quantitative competitive RT-PCR method we established that testosterone enhances in a dose-and time-related manner aromatase gene expression in PSs and RSs; 5α-DHT induces the same effect. Furthermore, testosterone increases the estradiol output in both germ cell populations whereas 5α-DHT was inefficient, therefore suggesting that the effect of androgens on P450 arom gene transcription was independent of estrogen formation. In fact estradiol inhibits the Cyp19 gene expression in PSs and RSs. ICI 182780, an estrogen receptor antagonist, has no effect on testosterone-stimulated aromatase expression in PSs and RSs. By contrast, ICI 182,780 suppresses the inhibitory effect of estradiol on P450 arom mRNA expression in PSs and RSs. Similarly, nilutamide, a non-steroidal anti-androgen specific for androgen receptors, abolishes the testosterone-stimulated aromatase expression in PSs and RSs. These observations show that androgens up-regulate aromatase gene expression in purified adult rat germ cells whereas estrogens exert an opposite effect, which may suggest the presence of androgen and estrogen responsive elements on the aromatase promoter(s).

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“…AR are colocalized in aromatase-positive cells but no estrogen receptor-α (ERα) can usually be detected in most of the cells expressing this enzyme in the POM or BST, although ERα are present in many adjacent cells of the same nuclei. It has been hypothesized that the effects of estrogens on aromatase transcription are mediated transynaptically [79]while androgens may act directly on the aromatase gene [80, 81, 82, 83]. Studies undertaken with in vitro systems have shown that the interactions of SRC-1 with ERα are stronger than with AR but the relative importance of this coactivator for the modulation of both estrogen and androgen receptor action in vivo remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

et al. 2002

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The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. Reducing the expression of SRC-1 by injection of specific antisense oligonucleotides markedly inhibits the effects of estrogens of the sexual differentiation of brain and behavior in rats and inhibits the activation of female sexual behavior in adult female rats. SRC-1 thus appears to be involved in both the development and activation of sexual behavior. In the Japanese quail brain, we amplified by RT-PCR a 3,411-bp fragment extending from the HLH domain to the activating domain-2 of the protein. The quail SRC-1 is closely related to the mammalian (m) SRC-1 and contains a high proportion of GC nucleotides (62.5%). Its amino acid sequence presents 70% identity with mammalian SRC-1 and contains the three conserved LXXLL boxes involved in the interaction with nuclear receptors. In both males and females, RT-PCR demonstrates a similarly high level of expression in the telencephalon, diencephalon, optic lobes, brain stem, spinal cord, pituitary, liver, kidney, adrenal gland, heart, lung, gonads and gonoducts. Males express significantly higher levels of SRC-1 in the preoptic area-hypothalamus than females. In both sexes, lower levels of expression are observed in the cerebellum and muscles. In situhybridization utilizing a mixture of four digoxigenin-labeled oligonucleotides confirms at the cellular level the widespread distribution of SRC-1 mRNA in the brain and a particularly dense expression in steroid-sensitive areas that play a key role in the control of male sexual behavior. These data confirm the presence and describe for the first time the SRC-1 distribution in the brain of an avian species. They confirm its broad, nearly ubiquitous, distribution in the entire body including the brain as could be expected for a coactivator that regulates to the action of many nuclear receptors. However this distribution is heterogeneous in the brain and sexually differentiated in at least some areas. The very dense expression of SRC-1 in limbic and mesencephalic nuclei that are associated with the control of male sexual behavior is consistent with the notion that this coactivator plays a significant role in the activation of this behavior.

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Region-Specific Regulation of Cytochrome P450 Aromatase Messenger Ribonucleic Acid by Androgen in Brains of Male Rhesus Monkeys1

Cited by 36 publications

References 32 publications

Regulation of cytochrome P450 aromatase gene expression in adult rat Leydig cells: comparison with estradiol production

Regulation of cytochrome P450 aromatase gene expression in adult rat Leydig cells: comparison with estradiol production

Steroids control the aromatase gene expression in purified germ cells from the adult male rat

Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

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