Androgen receptors are expressed in a variety of human fetal extragenital tissues: an immunohistochemical study

Sajjad, Yasmin; Quenby, Siobhán; Nickson, Paul; Lewis‐Jones, D. I.; Vince, Gill

doi:10.1111/j.1745-7262.2007.00320.x

Cited by 19 publications

(9 citation statements)

References 18 publications

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“…GAPDH has been reported to contribute to neurological disorder such as Huntington and Alzheimer diseases [52] which indicates GAPDH might not be an optimal candidate gene in hypothalamus. In addition, differences in signaling pathway might influence the result, for instance androgen receptor expression in hypothalamus is relatively high, whereas in kidney, this receptor showed very weak expression [53,54]. These might affect various signaling pathways under the testosterone influence [55].…”

Section: Discussionmentioning

confidence: 99%

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

et al. 2017

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Real-time quantitative PCR (qPCR) is the most reliable and accurate technique for analyses of gene expression. Endogenous reference genes are being used to normalize qPCR data even though their expression may vary under different conditions and in different tissues. Nonetheless, verification of expression of reference genes in selected studied tissue is essential in order to accurately assess the level of expression of target genes of interest. Therefore, in this study, we attempted to examine six commonly used reference genes in order to identify the gene being expressed most constantly under the influence of testosterone in the kidneys and hypothalamus. The reference genes include glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin beta (ACTB), beta-2 microglobulin (B2m), hypoxanthine phosphoribosyltransferase 1 (HPRT), peptidylprolylisomerase A (Ppia) and hydroxymethylbilane synthase (Hmbs). The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed using the software programs NormFinder, geNorm, BestKeeper, and rank aggregation. Results showed that Hmbs and Ppia genes were the most stably expressed in the hypothalamus. Meanwhile, in kidneys, Hmbs and GAPDH appeared to be the most constant genes. In conclusion, variations in expression levels of reference genes occur in kidneys and hypothalamus under similar conditions; thus, it is important to verify reference gene levels in these tissues prior to commencing any studies.

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Section: Discussionmentioning

confidence: 99%

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

et al. 2017

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“…AR is widely expressed in reproductive tissues of both males and females [60]. In developing first-trimester human embryos, expression of AR has been detected in several tissues, including several extragenital sites, such as thymus, bronchial epithelium of the lung, spinal cord, and cardiac valves [61]. AR levels in the fetal lung change significantly with gestational age during mid- and late gestation [62].…”

Section: Discussionmentioning

confidence: 99%

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

et al. 2012

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Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

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“…To allow for direct comparisons of our results to previous studies of AR expression in the external genitalia of developing mammals, the level of AR staining for each region was rated based on the following 0-3 scale: 0, no staining present; 1, mild staining (few positively stained cells); 2, moderate staining (approximately 20-50% of all cells in an area); and 3, abundant and intense staining (approximately 50-100% of cells in an area). This scale has been frequently used for evaluating region specific patterning of AR in developing mammalian reproductive tissues (Takane et al 1991;Sonea et al 1997;Kim et al 2002;Sajjad et al 2007). Evaluations of tissue staining were performed by two observers blind to the sex and age the animals.…”

Section: Experiments 1 and 2: Immunohistological Localization Of Ar Amentioning

confidence: 99%

Ancestral androgenic differentiation pathways are repurposed during the evolution of adult sexual plasticity

Schuppe

Solomon‐Lane

Pradhan

et al. 2016

Evolution and Development

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Although early exposure to androgens is necessary to permanently organize male phenotype in many vertebrates, animals that exhibit adult sexual plasticity require mechanisms that prevent early fixation of genital morphology and allow for genital morphogenesis during adult transformation. In Lythrypnus dalli, a teleost fish that exhibits bi-directional sex change, adults display dimorphic genitalia morphology despite the absence of sex differences in the potent fish androgen 11-ketotestosterone. Based on conserved patterns of vertebrate development, two steroid-based mechanisms may regulate the early development and adult maintenance of dimorphic genitalia; local androgen receptor (AR) and steroidogenic enzyme expression. Consistent with the ancestral pattern of AR expression during the multipotential phase of differentiation, juvenile differentiation into either sex involved high mesenchymal AR expression. In adults, AR expression was high throughout the male genitalia, but low or absent in females. Consistent with the hypothesis that adult sexual plasticity repurposes pathways from primary differentiation, we show that adults with transitioning genitalia also exhibited higher AR expression relative to females. Local androgen biosynthesis may also participate in genitalia transformation, as transitioning adults had greater 11β-HSD-like immunoreactivity in the epithelial layer of the dorsal lumen compared to both sexes. By administering an AR antagonist to adult males, we show AR is necessary to maintain male-typical morphology. In a species that is resistant to early sexual canalization, early androgenic differentiation mechanisms are consistent with other vertebrates and the tissue-specific regulation of AR expression appears to be repurposed in adulthood to allow for transitions between sexual phenotypes.

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Androgen receptors are expressed in a variety of human fetal extragenital tissues: an immunohistochemical study

Cited by 19 publications

References 18 publications

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

Ancestral androgenic differentiation pathways are repurposed during the evolution of adult sexual plasticity

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