Expression and regulation of steroid 5α-reductase in the genital tubercle of the fetal rat

Tian, Hui; Russell, David W.

doi:10.1002/(sici)1097-0177(199705)209:1<117::aid-aja11>3.0.co;2-z

Cited by 22 publications

(11 citation statements)

References 21 publications

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“…Endogenous peroxidase activity was blocked with 3% hydrogen peroxide in methanol for 10 min, and antigen retrieval was achieved by treatment with 0.5% trypsin at 37°C for 15 min. Rabbit polyclonal antibody against a 25-amino-acid segment of the human 5α-reductase type 2 protein was used (Tian and Russell 1997). The specificity of the AR immunohistochemical staining was confirmed by the use of positive (prostate) and negative controls (uterus; data not shown).…”

Section: Preparation Of the Human Tissuesmentioning

confidence: 89%

“…To improve our understanding of the role of androgens in human male fetal urethral development, it is necessary to know the distribution of the AR and 5α-reductase type 2 in the developing external genitalia. Several studies have been performed in animals (Veyssiere et al 1985;Cooke et al 1991;Tsuji et al 1994;Bentvelsen et al 1995;Tian and Russell 1997); however, complete data are lacking in human tissues, and prior studies have not focused on urethral development in the human fetus (Kalloo et al 1993;Levine et al 1996).…”

Section: Introductionmentioning

confidence: 99%

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Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra

et al. 2001

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Normal penile development is dependent on testosterone, its conversion via steroid 5 alpha-reductase type 2 to dihydrotestosterone, and a functional androgen receptor (AR). The goal of this study was to investigate the distribution of AR and 5 alpha-reductase type 2 in the developing human fetal external genitalia with special emphasis on urethra formation. Twenty fetal genital specimens from normal human males (12-20 weeks gestation) were sectioned serially and stained by avidin-biotinylated peroxidase complex method with antigen retrieval. Stained sections throughout male genital development documented the expression of AR and 5 alpha-reductase type 2 in the phallus. Between 12 and 14 weeks of gestation, AR was localized to epithelial cells of the urethral plate in the glans, the tubular urethra of the penile shaft, and stromal tissue surrounding the urethral epithelium. In the fetal penis between 16 and 20 weeks gestation, the density of AR expression was greatest in urethral epithelial cells versus the surrounding stromal tissues. There was a characteristic pattern of AR expression in the glandular urethral epithelium between 16 and 20 weeks gestation. AR expression was greater along the ventral aspect of the glandular urethra than along the dorsal aspect of the urethral epithelium. The expression of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra, especially along the urethral seam area in the ventral portion of the remodeling urethra. These anatomical studies support the hypothesis that androgens are essential for the formation of the ventral portion of the urethra and that abnormalities in either the AR or 5 alpha-reductase type 2 can explain the occurrence of hypospadias.

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Section: Preparation Of the Human Tissuesmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra

et al. 2001

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“…Androgens such as testosterone (T) and dihydrotestosterone (DHT) are essential inducers for masculinization of male reproductive organs. T is locally converted into the DHT by 5a-reductase type 2 (Tian & Russell 1997;Kim et al 2002). Medical textbooks describe that DHT is generally one of the major androgens acting on male-type GT differentiation (Park 2011;Snodgrass 2011).…”

Section: Introductionmentioning

confidence: 99%

Systematic analyses of murine masculinization processes based on genital sex differentiation parameters

Suzuki

Yamada

2015

Dev Growth Differ

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Murine reproductive tissues of the external genitalia and perineum develop with remarkably distinctive characteristics in males and females. Although many researches on such mouse organ development have been reported, there are still limited parameters that evaluate the developmental sexual differences of external genitalia and perineum. Furthermore, elucidation of the recent developmental signals for the external genitalia and perineum requires up-to-date knowledge of gene functions in reproductive science. To promote researches on reproductive organ formation, establishment of parameters for the androgen-mediated formation of external genitalia and perineum is essential. In this study, we propose genital sex differentiation parameters (GSDP), a set of developmental parameters based on systematic three-dimensional tissue reconstruction and cumulative histological analyses. We define the sexual differences of external genitalia and perineum by GSDP through analyzing mouse models, androgen inhibitor-induced feminization experiments and Mafb mutant mouse with defective urethral differentiation. The urethral parameters displayed prominent reduction by the androgen inhibitor (finasteride) treatment. However, genital tubercle (GT) size parameters were not affected by such treatment. These results indicated that sensitivity to dihydrotestosterone was different between embryonic GT size and urethral formation. Furthermore, we evaluated the extent of urethral defects of Mafb mutant mice by GSDP. Thus, GSDP is a set of useful parameters to define the sexual differences during external genitalia and perineum development.

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“…Pregnant mice were killed by cervical dislocation at the time intervals indicated, and the embryos were dissected, fixed in 4% paraformaldehyde, and embedded in paraffin. Serial sagittal sections of 4 m thickness were prepared using a microtome (44). To determine the sex of each embryo, a small aliquot of tissue was taken from the yolk sac and placed in 500 l of 50 mM KCl, 1.5 mM MgCl 2 , 10 mM Tris HCl, pH 8.5, 0.01% (wt/vol) gelatin, 0.45% (vol/vol) NP40, 0.45% (vol/vol)Tween 20, and 100 g/ml proteinase K (Sigma Chemical Co.) at 55 C overnight.…”

Section: Animalsmentioning

confidence: 99%

“…In situ hybridization was performed as previously described (44). A 2.4-kb fragment containing the mouse SR-BI cDNA (kindly provided by Dr. Monty Krieger, Massachusetts Institute of Technology, Cambridge, MA) was subcloned into pcDNA3 (Invitrogen, Carlsbad, CA).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Developmental and Hormonal Regulation of Murine Scavenger Receptor, Class B, Type 1

Cao¹,

Zhao²,

Stangl³

et al. 1999

Molecular Endocrinology

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The scavenger receptor, class B, type I (SR-BI), is the predominant receptor that supplies plasma cholesterol to steroidogenic tissues in rodents. We showed previously that steroidogenic factor-1 (SF-1) binds a sequence in the human SR-BI promoter whose integrity is required for high-level SR-BI expression in cultured adrenocortical tumor cells. We now provide in vivo evidence that SF-1 regulates SR-BI. During mouse embryogenesis, SR-BI mRNA was initially expressed in the genital ridge of both sexes and persisted in the developing testes but not ovary. This sexually dimorphic expression profile of SR-BI expression in the gonads mirrors that of SF-1. No SR-BI mRNA was detected in the gonadal ridge of day 11.5 SF-1 knockout embryos. Both SR-BI and SF-1 mRNA were expressed in the cortical cells of the nascent adrenal glands. These studies directly support SF-1 participating in the regulation of SR-BI in vivo. We examined the effect of cAMP on SR-BI mRNA and protein in mouse adrenocortical (Y1-BS1) and testicular carcinoma Leydig (MA-10) cells. The time courses of induction were strikingly similar to those described for other cAMP- and SF-1-regulated genes. Addition of lipoproteins reduced SR-BI expression in Y1-BS1 cells, an effect that was reversed by administration of cAMP analogs. SR-BI mRNA and protein were expressed at high levels in the adrenal glands of knockout mice lacking the steroidogenic acute regulatory protein; these mice have extensive lipid deposits in the adrenocortical cells and high circulating levels of ACTH. Taken together, these studies suggest that trophic hormones can override the suppressive effect of cholesterol on SR-BI expression, thus ensuring that steroidogenesis is maintained during stress.

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Expression and regulation of steroid 5α-reductase in the genital tubercle of the fetal rat

Cited by 22 publications

References 21 publications

Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra

Expression of the androgen receptor and 5α-reductase type 2 in the developing human fetal penis and urethra

Systematic analyses of murine masculinization processes based on genital sex differentiation parameters

Developmental and Hormonal Regulation of Murine Scavenger Receptor, Class B, Type 1

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