[Bilateral autogenous transplantation of impacted maxillary canines]. / Bilaterale autologe transplantatie van geïmpacteerde maxillaire cuspidaten.

In a fifteen-year-old girl, bilaterally impacted permanent maxillary canines were established. A difficult palatinal placement and an apical deviation were found in both teeth. Surgical exposure of the canines, followed by orthodontic traction was not desirable. Both remaining primary canines showed signs of resorption. Autogenous transplantation of the maxillary canines was the treatment chosen.

Expression of Estrogen Sulfotransferase 1E1 and Steroid Sulfatase in Breast Cancer: A Immunohistochemical Study.

It is known that the steroid sulfatase (STS) and the estrogen sulfotransferase (EST1E1) are commonly expressed in human breast carcinomas. STS and EST1E1 combined action could maintain the equilibrium between sulfated (inactive) and unconjugated (active) estrogens, which might have effects on development of hormone dependent breast cancer.We studied the expression of the STS and EST1E1 in 88 breast carcinomas and 57 adjacent non-malignant tissues by immunohistochemistry. The results were correlated with the tumor expression of estrogen receptor α (ER-α) and ß (ER-ß), progesterone receptor A (PR-A) and B (PR-B) and the proliferation marker CDC47, the tumoral type and stage and the age at surgery.STS expression was higher in carcinoma specimens than in adjacent normal tissues, although not to a significant level (p = 0.064) and it was positively associated with CDC47 expression (p < 0.05). These observations support the hypothesis that STS is overexpressed in breast cancer and associated with a worse prognosis.EST1E1 was observed for the first time in the nuclei of epithelial and tumoral cells. Tumor expression of EST1E1 was positively correlated with ER-ß (p < 0.01) and PR-B (p < 0.05), two steroid receptors already associated with an improve prognosis for breast cancer.Controlling the STS overexpression in carcinomas could be a way to inhibit cancer growth. The significance of the association between EST1E1 and ER-ß or PR-B should be further studied since these two receptors are transcription activators and may regulate the expression of protective enzymes like EST1E1.

Pangenomic changes induced by DHEA in the skin of postmenopausal women.

The objective of this study was to explore, for the first time, the changes in the pangenomic profile induced in human skin in women treated with dehydroepiandrosterone (DHEA) applied locally. Sixty postmenopausal women participated in this phase II prospective, randomized, double-blind and placebo-controlled study. Women were randomized to the twice daily local application of 0% (placebo), 0.3%, 1% or 2% DHEA cream. Changes in the pangenomic expression profile were studied using Affymetrix Genechips. Significant changes (p<0.05) in sixty-six DHEA-responsive probe sets corresponding to 52 well-characterized genes and 9 unknown gene sequences were identified. A dose-dependent increase in the expression of several members of the collagen family was observed, namely COL1, COL3 and COL5 as well as the concomitant modulation of SPARC, a gene required for the normal deposition and maturation of collagen fibrils in the dermis. Several genes involved in the proliferation and differentiation of keratinocytes were also modulated. In addition, topical DHEA reduced the expression of genes associated with the terminal differentiation and cornification of keratinocytes. Our results strongly suggest the possibility that DHEA could exert an anti-aging effect in the skin through stimulation of collagen biosynthesis, improved structural organization of the dermis while modulating keratinocyte metabolism.

Expression of 17beta-hydroxysteroid dehydrogenase type 2 and type 5 in breast cancer and adjacent non-malignant tissue: a correlation to clinicopathological parameters.

Estrogens play an important role in the development and progression of breast cancer. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) type 2 and type 5 are involved in sex steroid metabolism. 17beta-HSD type 2 converts estradiol to estrone while 17beta-HSD type 5 converts androstenedione to testosterone. Using immunocytochemistry, we have studied the expression of 17beta-HSD type 2 and type 5 in 50 specimens of breast carcinoma and adjacent non-malignant tissues. The results were correlated with the estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor A (PRA) and B (PRB), androgen receptor and CDC47 and with the tumor stage, tumor size, nodal status and menopausal status. 17beta-HSD type 2 was expressed in 20% and 17beta-HSD type 5 in 56% of breast cancer specimens. In adjacent normal tissues, both enzymes were highly expressed in almost all the patients. No significant association could be found between the expression of 17beta-HSD type 2 and 17beta-HSD type 5 and between the expression of each enzyme and the clinicopathological parameters studied. The decrease in 17beta-HSD type 2 and 17beta-HSD type 5 expressions in breast cancer may play a predominant role in the development and/or progression of the cancer by modifying the intratumoral levels of estrogens and androgens.

Oestrogenic regulation of pro-opiomelanocortin, neuropeptide Y and corticotrophin-releasing hormone mRNAs in mouse hypothalamus.

It is well documented that oestrogen suppresses food intake by an action at the hypothalamic level. Using in situ hybridisation, we studied the effect of castration (CX) and short-term administration of oestradiol (E2) in CX female mice for three neuropeptides involved in feeding behaviour: two anorexigenic peptides, (i) the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone and (ii) corticotrophin-releasing hormone (CRH), and the orexigenic peptide, (iii) neuropeptide Y (NPY). POMC-expressing neurones were mostly laterally located in the arcuate nucleus. POMC mRNA expression was decreased following CX and a single injection of E2 induced an increase in mRNA levels at 12- and 24-h time intervals. In the parvocellular area of the paraventricular nucleus, CRH mRNA levels were similarly decreased after CX and completely restored to normal levels at 12 and 24 h following E2 injection. On the other hand, the levels of NPY mRNA expressed in neurones located in the inner zone of the arcuate nucleus were increased by CX and decreased to the levels observed in intact animals by E2 injection (3-24 h). The present data suggest that oestrogen might exert an anorexigenic action by stimulating POMC and CRH mRNA expression and decreasing NPY mRNA expression in the hypothalamus.

Localization and glucocorticoid regulation of 11beta-hydroxysteroid dehydrogenase type 1 mRNA in the male mouse forebrain.

The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts the inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone. There is accumulating evidence indicating widespread expression of 11beta-HSD1 in the brain. However, there is little information about regulation of 11beta-HSD1 expression in this tissue. Using in situ hybridization involving use of 35S-labeled cRNA probe, we have studied the distribution of cells expressing 11beta-HSD1 mRNA in the male mouse forebrain as well as the effects of adrenalectomy (ADX) and acute administration of corticosterone (3 and 24 h) on 11beta-HSD1 mRNA levels. Cells expressing 11beta-HSD1 mRNA were mostly detected in the cerebral cortex, hippocampus, amygdala and medial preoptic area, with the highest expression in the cerebral cortex (retrosplenial granular area) and hippocampus (CA3 and granular layer of the gyrus dentatus). Seven days following ADX, 11beta-HSD mRNA levels were increased by 50% in the gyrus dentatus, by 100% in the CA3 area, and 105% in the cerebral cortex. Administration of corticosterone to ADX mice induced a significant decrease in mRNA, in both the hippocampus and cerebral cortex so that, at the 24 h time interval, the levels were similar to those observed in intact mice. These results clearly indicate that circulating corticosterone is downregulating the expression of 11beta-HSD1 mRNA in the two forebrain areas studied. This downregulation might contribute to maintain low intracellular corticosterone levels in central regions and then prevent the deleterious effects induced by high glucocorticoid levels.

Expression of sulfotransferase 1E1 in human prostate as studied by in situ hybridization and immunocytochemistry.

BACKGROUND: Estrogen is recognized to play a role in the development and function of the prostate. Estrogen sulfotransferase (EST) 1E1 catalyzes the sulfoconjugation of estrogen and is thus involved in the metabolism of estrogen. We have recently shown that EST 1E1 is highly expressed in male mouse reproductive organs, including prostate. It appeared of interest to study the expression of EST 1E1 in human prostate. METHODS: EST 1E1 mRNA and protein expression was evaluated in benign prostatic hyperplasia (BPH) using in situ hybridization and immunocytochemistry, respectively. RESULTS: EST 1E1 mRNA and protein were found to be expressed in epithelial cells bordering alveola lumen (luminal cells) as well as stroma cells. CONCLUSION: The enzyme EST may play a physiological role in regulating local estrogen levels in human prostate.

Role of androgens and glucocorticoids in the regulation of diazepam-binding inhibitor mRNA levels in male mouse hypothalamus.

In peripheral organs, gonadal and adrenal steroids regulate diazepam-binding inhibitor (DBI) mRNA expression. In order to further investigate the involvement of peripheral steroid hormones in the modulation of brain DBI mRNA expression, we studied by semiquantitative in situ hybridization the effect of adrenalectomy (ADX) and castration (CX) and short-term replacement therapy on DBI mRNA levels in the male mouse hypothalamus. Cells expressing DBI mRNA were mostly observed in the arcuate nucleus, the median eminence and the ependyma bordering the third ventricle. In the median eminence and the ependyma bordering the third ventricule, the DBI gene expression was decreased in ADX rats and a single injection of corticosterone to ADX rats induced a significant increase in DBI gene expression at 3 and 12 h time intervals without completely restoring the basal DBI mRNA expression observed in intact mice. In the arcuate nucleus, ADX and corticosterone administration did not modify DBI mRNA expression. CX down-regulated DBI gene expression in the ependyma bordering the third ventricle. The administration of dihydrotestosterone (3-24 h) completely reversed the inhibitory effect of CX. In the median eminence and arcuate nucleus, neither CX or dihydrotestosterone administration modified DBI mRNA levels. These results suggest that the effects of glucocorticoids on the hypothalamo-pituitary-adrenocortical axis and androgens on the hypothalamo-pituitary-gonadal axis are mediated by DBI.

Expression of aromatase and 17beta-hydroxysteroid dehydrogenase types 1, 7 and 12 in breast cancer. An immunocytochemical study.

It is known that there is a local biosynthesis of estradiol (E2) in breast carcinoma. The steroidogenic enzymes involved in E2 formation are aromatase which transforms testosterone into E2 and androstenedione into estrone (E1) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) which convert E1 into E2. Using immunocytochemistry, we have studied the expression of aromatase and the three reductive 17beta-HSDs 17beta-HSD types 1, 7 and 12 in 41 specimens of female human breast carcinoma and adjacent non-malignant tissues. These results were correlated with the estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor, androgen receptor, CDC47 and c-erb B-2 expressions and with the tumor stages. Aromatase was found in 58%, 17beta-HSD type 7 in 47% and 17beta-HSD type 12 in 83% of the breast cancer specimens. The 17beta-HSD type 1 could be detected in only one tumor. A significant correlation was observed between the aromatase, 17beta-HSD type 7 and 17beta-HSD type 12 expression, as well as between each of the two enzymes 17beta-types 7 and 12 and the ERbeta expression. The expression of 17beta-HSD type 12 was significantly higher in breast carcinoma specimens than in normal tissue. There was also a significant association of CDC 47 expression with ERbeta, AR and 17beta-HSD type 12. The results indicate that aromatase, 17beta-HSD type 7 and 17beta-HSD type 12, but not 17beta-HSD type 1, are commonly expressed in human breast cancer. Moreover, the high expression of both 17beta-HSD type 12 and ERbeta in breast carcinoma cells may play a role in the development and/or progression of breast cancer.

AffyMiner: mining differentially expressed genes and biological knowledge in GeneChip microarray data.

BACKGROUND: DNA microarrays are a powerful tool for monitoring the expression of tens of thousands of genes simultaneously. With the advance of microarray technology, the challenge issue becomes how to analyze a large amount of microarray data and make biological sense of them. Affymetrix GeneChips are widely used microarrays, where a variety of statistical algorithms have been explored and used for detecting significant genes in the experiment. These methods rely solely on the quantitative data, i.e., signal intensity; however, qualitative data are also important parameters in detecting differentially expressed genes. RESULTS: AffyMiner is a tool developed for detecting differentially expressed genes in Affymetrix GeneChip microarray data and for associating gene annotation and gene ontology information with the genes detected. AffyMiner consists of the functional modules, GeneFinder for detecting significant genes in a treatment versus control experiment and GOTree for mapping genes of interest onto the Gene Ontology (GO) space; and interfaces to run Cluster, a program for clustering analysis, and GenMAPP, a program for pathway analysis. AffyMiner has been used for analyzing the GeneChip data and the results were presented in several publications. CONCLUSION: AffyMiner fills an important gap in finding differentially expressed genes in Affymetrix GeneChip microarray data. AffyMiner effectively deals with multiple replicates in the experiment and takes into account both quantitative and qualitative data in identifying significant genes. AffyMiner reduces the time and effort needed to compare data from multiple arrays and to interpret the possible biological implications associated with significant changes in a gene's expression.

Is dehydroepiandrosterone a hormone?

Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.

Bone microenvironment-related growth factors, zoledronic acid and dexamethasone differentially modulate PTHrP expression in PC-3 prostate cancer cells.

Bone metastasis microenvironment-related growth factors such as insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-beta1), basic fibroblast growth factor (bFGF) and interleukin 6 (IL-6) show survival factor activity, thereby inhibiting chemotherapy-induced apoptosis of PC-3 prostate cancer cells in vitro. Recently, zoledronic acid has been shown to induce apoptosis in PC-3 prostate cancer cells while overexpression of parathyroid hormone-related protein (PTHrP) inhibits serum deprivation-induced apoptosis in PC-3 cells. Consequently, we have investigated whether IGF-1, TGF-beta1, bFGF, IL-6, zoledronic acid and/or dexamethasone affect the expression of the PTHrP and type I PTH/PTHrP receptor (PTH.1R) in PC-3 prostate cancer cells using relative quantitative PCR and real-time PCR (expression at mRNA level) and immunocytochemical and immunofluorescence analysis (expression at protein level). Our data show that IGF-1, TGF-beta1, bFGF and IL-6 increase PTHrP mRNA expression and its perinuclear localization, while zoledronic acid (50 muM, 100 muM for 24 h and 48 h) and dexamethasone suppress PTHrP expression in PC-3 cells. We did not detect any appreciable change of the PTH.1R expression due to IGF-1, TGF- beta1, bFGF, IL-6, zoledronic acid or dexamethasone in PC-3 cells. Therefore, it is conceivable that bone metastasis microenvironment-related survival factor/anti-apoptotic activity and zoledronic acid anticancer action/pro-apoptotic activity on PC-3 cells is mediated, at least in part, by differential modulation of PTHrP expression.

Localization of type 5 17beta-hydroxysteroid dehydrogenase mRNA in mouse tissues as studied by in situ hybridization.

The mouse enzyme type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD) catalyzes the conversion of androstenedione to testosterone and, to a lesser degree, the conversion of estrone to estradiol. In order to determine the exact sites of action of type 5 17beta-HSD, we studied the cellular localization of the mRNA of the enzyme in mouse tissues by using in situ hybridization. Specific hybridization signal was found in the liver, ovary, adrenal cortex, and kidney. In the liver of mice of both sexes, a strong signal was observed in all hepatocytes. In the ovary, specific labeling was detected in the granulosa and theca interna cells in growing follicles and in luteal cells. In the female adrenal cortex, intense labeling was restricted to the zona reticularis, whereas no type 5 17beta-HSD mRNA expression could be found in the male adrenal cortex. In the kidney of mice of both sexes, type 5 17beta-HSD mRNA was expressed in epithelial cells in both the proximal and distal convoluted tubules. The data indicate that androgens and estrogens are formed via the action of type 5 17beta-HSD in specific cell types in the liver, ovary, adrenal cortex, and kidney.

Androgenic down-regulation of urotensin II precursor, urotensin II-related peptide precursor and androgen receptor mRNA in the mouse spinal cord.

We had previously shown that in rat spinal cord motoneurons urotensin II (UII) precursor mRNA was down-regulated by androgens. Very recently, a gene encoding the precursor of a UII analog, termed UII-related peptide (URP), has been identified. Using in situ hybridization, we studied the localization of UII and URP precursor as well as androgen receptor (AR) mRNA in the male mouse thoracic spinal cord. We also evaluated the androgenic regulation of the two peptide precursor and AR mRNA expression in the ventral horn of the mouse thoracic spinal cord. The results revealed that URP precursor mRNA was localized in motoneurons and that the vast majority of the motoneurons expressed both peptide precursor as well as AR mRNA. Seven-day castration induced an increase in UII and URP precursor and AR mRNA levels. Short term (3-24 h) administration of dihydrotestosterone to castrated animals restored the three protein mRNA levels to the levels observed in intact animals. These results suggest that in the ventral horn of the mouse spinal cord both UII and URP precursor and AR mRNA are expressed by the same neurons and that circulating androgens are exerting a down-regulation of the three protein mRNA expression, possibly by a direct action on motoneurons.

Localization of type 7 17beta-hydroxysteroid dehydrogenase in mouse tissues. In situ hybridization studies.

The enzyme type 7 17beta-hydroxysteroid dehydrogenase (17beta-HSD) selectively catalyzes the conversion of estrone (E1) into estradiol (E2). In order to obtain detailed information about the exact sites of action of type 7 17beta-HSD, we have studied the cellular localization of type 7 17beta-HSD mRNA in mouse tissues using in situ hybridization (ISH). In parallel studies, we also measured the enzyme mRNA levels by quantitative real time (RT)-PCR. In the ovary, strong hybridization signal was restricted to corpus luteum cells. In the female mammary gland, type 7 17beta-HSD mRNA was found to be expressed in stromal cells surrounding the ducts. In the clitoral and preputial glands, specific labeling was observed in the epithelial cells of both acini and small ducts. In the adrenal gland, hybridization signal was observed in the zona fasciculata and reticularis in the cortex. In the liver, hybridization signal was found in all the hepatocytes. In the colon, type 7 17beta-HSD mRNA expression was restricted to epithelial cells of the mucosa. From the results obtained with quantitative real time RT-PCR, it appears, with a very few exceptions, that in tissues exhibiting low mRNA expression no ISH signal could be detected. The present data suggest that E2 can be formed through the action of type 7 17beta-HSD in specific cell types in the ovary and peripheral tissues, in addition to type 1 17beta-HSD, thus providing tissues with an alternative route of formation of E2.

Localization of 17beta-hydroxysteroid dehydrogenase type 1 mRNA in mouse tissues.

The enzyme 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 catalyzes the conversion of estrone (E1) into 17beta estradiol (E2). To gain information about the cellular localization of 17beta-HSD mRNA type 1 expression, we performed in situ hybridization using a 35S-labeled cRNA probe in several tissues of adult mice of both sexes. In the ovary, high expression was found in granulosa cells of growing follicles. No specific labeling could be observed in corpora lutea or interstitial cells. In the pituitary gland of animals of both sexes, 17beta-HSD type 1 mRNA was expressed in the intermediate lobe melanotrophs while no specific signal could be detected in the anterior or posterior lobes of the pituitary. In the prostate, 17beta-HSD type 1 mRNA was exclusively found in the epithelial cells. In both male and female mouse dorsal skin, a specific hybridization signal was seen in the sebaceous glands while the epidermis, stroma, hair follicles and sweat glands were unlabeled. In the testis, a hybridization signal was detected in germ cells of the seminiferous tubules, Leydig cells being unlabeled. The present data indicate that E2 can be formed through the action of 17beta-HSD type 1 in specific cells of the gonads and peripheral tissues. In the testes and peripheral tissues, the action of E2 is probably limited to the cells involved in its formation in an intracrine fashion.

Cellular localization of mRNA expression of enzymes involved in the formation and inactivation of hormonal steroids in the mouse prostate.

It is well documented that several tissues, including the prostate, are actively involved in the local formation and inactivation of hormonal steroids. To identify the cell types involved in the formation and inactivation of androgens and estrogens in the ventral lobe prostate, we have localized by in situ hybridization (ISH) a large number of steroidogenic as well as steroid-inactivating enzyme mRNAs in the adult mouse prostate. In parallel studies, we also measured enzyme mRNA levels by quantitative real-time PCR (RT-PCR) in ventral lobe prostates. From the results obtained with quantitative RT-PCR, it appears that, with a few exceptions, the enzyme with low mRNA expression could not be detected by ISH. The following enzymes have been localized by ISH: 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 3, 4, 7, 8, 9, 10, and 11; 5alpha-reductase type 2; 5beta reductase type 1; P450 7alpha hydroxylase; estrogen sulfotransferase type 1; 11beta-HSD types 1 and 2; and UDP-glucuronosyltransferase 1A6. All of these mRNAs are expressed in the epithelial cells of prostatic acini. Several enzyme mRNAs were also localized in stromal cells. Types 1, 7, and 10 17beta-HSD, estrogen sulfotransferase type 1, and 11beta-HSD types 1 and 2 were found only in epithelial cells. The present results indicate that both epithelial and stromal cells in the mouse prostate play a role in local formation and inactivation of hormonal steroids.

Localization of 20alpha-hydroxysteroid dehydrogenase mRNA in mouse brain by in situ hybridization.

The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone into its inactive form, 20alpha-hydroxyprogesterone. We studied the expression of 20alpha-HSD mRNA in mouse brain by in situ hybridization. 20alpha-HSD mRNA was exclusively found in neurons in cortex and hippocampus. In the cortex, the labelled cells were concentrated in the external granular layer, the external pyramidal layer and the inner granular layer. In the hippocampus, the labelling was mostly located over pyramidal cells of the CA1 layer. These results suggest that progesterone can be inactivated by 20alpha-HSD in some specific brain areas.

The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells.

Steroid hormones synthesized from cholesterol in the adrenal gland are important regulators of many physiological processes. It is now well documented that the expression of many genes required for steroid biosynthesis is dependent on the coordinated expression of the nuclear receptor steroidogenic factor-1 (SF-1). However, transcriptional mechanisms underlying the species-specific, developmentally programmed and hormone-dependent modulation of the adrenal steroid pathways remain to be elucidated. Recently, we demonstrated that the transcriptional regulating protein of 132 kDa (TReP-132) acts as a coactivator of SF-1 to regulate human P450scc gene transcription in human adrenal NCI-H295 cells. The present study shows that overexpression of TReP-132 increases the level of active steroids produced in NCI-H295 cells. The conversion of pregnenolone to downstream steroids following TReP-132 expression showed increased levels of glucocorticoids, C(19) steroids and estrogens. Correlating with these data, TReP-132 increases P450c17 activities via the induction of transcript levels and promoter activity of the P450c17 gene, an effect that is enhanced in the presence of cAMP or SF-1. In addition, P450aro activity and mRNA levels are highly induced by TReP-132, whereas 3beta-hydroxysteroid dehydrogenase type II and P450c11aldo transcript levels are only slightly modulated. Taken together, these results demonstrate that TReP-132 is a trans-acting factor of genes involved in adrenal glucocorticoid, C(19) steroid and estrogen production.

Localization and estrogenic regulation of androgen receptor mRNA expression in the mouse uterus and vagina.

Androgen receptors (AR) are highly expressed in female reproductive organs. In order to define the possible involvement of estrogens in the regulation of AR expression in the uterus and vagina, we have studied the effect of short-term administration of 17beta-estradiol (E2) to ovariectomized adult mice on AR mRNA levels. Seven days after ovariectomy, the mice received a single injection of E2 (0.05 microg/mouse) 3, 12 or 24 h before they were killed. The levels of AR mRNA were measured in the different uterine and vaginal compartments using quantitative in situ hybridization. In the uterus, AR mRNA was expressed in the luminal and glandular epithelial cells, stromal cells and smooth muscle cells. In the vagina, AR mRNA was localized in both epithelial and stromal cells. In the uterus after ovariectomy, AR mRNA levels were decreased by 18% in the epithelial cells, 23% in the stromal cells and 50% in the myometrial cells. AR mRNA levels were completely restored as early as 3 h after E2 administration in the epithelium and stroma, and at the 12-h time-interval in the myometrium. In the vaginal epithelium, ovariectomy induced a 70% decrease in AR mRNA expression. No effect could be detected 3 h after E2 administration, while at the longest time-intervals (12 and 24 h) there was an increase in mRNA levels corresponding to 70% of the levels observed in intact animals. In the vaginal stroma, ovariectomy was responsible for a 55% decrease in mRNA levels. While no significant changes were observed at the 3-h time-interval, a complete restoration of AR mRNA levels in stromal cells could be recorded at the longest time-intervals after E2 administration. The data obtained indicated that, in adult mice, estrogens exert a positive regulation of AR mRNA expression in the different compartments of both the uterus and the vagina.