Developmental pattern and regulation by androgens of androgen receptor expression in the urogenital tract of the rat

Bentvelsen, F.M.; Brinkmann, Albert O.; Schoot, P. van der; Linden, Jennifer; Kwast, Theodorus H. van der; Boersma, W.J.A.; Schröder, Fritz H.; Nijman, J. M.

doi:10.1016/0303-7207(95)03593-v

Cited by 93 publications

(57 citation statements)

References 20 publications

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“…This difference can be explained as follows. Androgen receptors do not begin to increase until a fetal age of about 14 days (Price and Ortiz, 1965;Bentvelsen et al, 1995). In the preimplantation embryo, androgen receptor protein expression and sex-related development have not yet started.…”

Section: Discussionmentioning

confidence: 99%

Effects of Flutamide on Sex Maturation and Behavior of Offspring Born to Female Rats Treated During Late Pregnancy

et al. 2004

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-Flutamide, when administered subcutaneously to female rats at doses of 3, 10, or 30 mg/ kg/day during late pregnancy (gestational days 16-21), significantly and dose-dependently decreased anogenital distance (AGD) of the male offspring in each dose group compared to controls. Significant delays in preputial separation were found in males at a dose of 30 mg/kg, but body weight gain was not inhibited. Cryptorchidism and absence of the prostate gland and seminal vesicles were found in males at doses ≥ 10 mg/kg, and testicular hypoplasia at a dose of 30 mg/kg. Hypospadias was noted in all dose groups and vaginal pouches at doses of ≥ 10 mg/kg. The effects on the accessory reproductive organs were severe, although the effects on the testes themselves were mild. However, those effects appeared to become more pronounced with growth, as evaluated on Days 30 and 42 and Weeks 16 to 18. Most of these affected animals displayed cryptorchidism. Male offspring exposed to flutamide in utero showed impairments of sexual behavior as adults in a dose-related manner. Number and frequency of mounts with intromissions was markedly decreased in all treated groups as compared to controls. At 10 mg/kg, no mounting with ejaculation was observed, and at a dose of 30 mg/kg, no mounting with intromission or ejaculation was observed. These changes in sexual behavior were closely associated with abnormalities of the external genitalia. Animals with hypospadias did not display mounts with ejaculation. However, F1 males that copulated at a dose of 3 mg/kg had a normal reproductive function. Histological examination of the reproductive organs revealed degeneration of the seminiferous tubules, hypospermatogenesis, and hypoplasia and inflammation of the seminal vesicles and prostate. Serum levels of FSH, LH, and testosterone in these animals were comparable between control and all dose groups. Therefore, the male reproductive dysfunction seen in the present study could not be attributed to abnormal sex hormone levels during maturation, but to possible demasculinization of the brain and progressively delayed dysmorphorogy of the male genitalia caused by fetal exposure to flutamide.

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Section: Discussionmentioning

confidence: 99%

Effects of Flutamide on Sex Maturation and Behavior of Offspring Born to Female Rats Treated During Late Pregnancy

et al. 2004

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“…It is suggested that testosterone reaches the Wolffian duct bound to androgen binding protein (ABP), indicating that this protein may be important to the maintenance of high androgen levels in the proximal region of the duct when compared to the remaining tissue (46). In the rat, the Wolffian duct first expresses AR in the mesenchymal cells at embryonic day 14-15 and (44,47). Testosterone reaching the Wolffian duct by the luminal compartment up regulates AR levels and induces proliferation of the epithelial cells through mesenchymal-epithelial cell interactions involving paracrine factors (48).…”

Section: Expression and Physiological Roles Of Androgen Receptor In Tmentioning

confidence: 99%

Androgens and the male reproductive tract: an overview of classical roles and current perspectives

Patrão

Silva

Avellar

2009

Arq Bras Endocrinol Metab

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Androgens are steroid hormones that play key roles in the development and maintenance of male phenotype and reproductive function. These hormones also affect the function of several non-reproductive organs, such as bone and skeletal muscle. Endogenous androgens exert most of their effects by genomic mechanisms, which involve hormone binding to the androgen receptor (AR), a ligand-activated transcription factor, resulting in the modulation of gene expression. AR-induced non-genomic mechanisms have also been reported. A large number of steroidal and non-steroidal AR-ligands have been developed for therapeutic use, including the treatment of male hypogonadism (AR agonists) and prostate diseases (AR antagonists), among other pathological conditions. Here, the AR gene and protein structure, mechanism of action and AR gene homologous regulation were reviewed. The AR expression pattern, its in vivo regulation and physiological relevance in the developing and adult testis and epididymis, which are sites of sperm production and maturation, respectively, were also presented. Arq Bras Endocrinol Metab. 2009;53(8):934-45Keywords Androgen receptor; male reproductive tract; testis; epididymis RESUMOOs androgênios são hormônios esteroides com papel fundamental no desenvolvimento e na manutenção do fenótipo masculino e da função reprodutiva. Esses hormônios também afetam a função de diversos tecidos não reprodutivos, como, por exemplo, o ósseo e musculoesquelé-tico. Os androgênios endógenos exercem a maioria de suas funções por mecanismo genômico, que envolve a ligação do hormônio ao receptor de androgênio (RA), um fator de transcrição ativado por ligante, o que resulta no controle da expressão gênica. Mecanismos não genômicos também têm sido associados aos efeitos induzidos pelo RA. Um grande número de ligantes do RA, esteroidais e não esteroidais, tem sido desenvolvido para o uso terapêutico, incluindo o tratamento do hipogonadismo masculino (agonistas do RA) e de doenças da próstata (antagonistas do RA), entre outras condições patológicas. Neste trabalho, foram discutidas as caracterís-ticas estruturais básicas do RA (gene e proteína), os mecanismos de ação desse receptor, bem como aspectos relacionados à sua regulação homóloga. O padrão de expressão do RA, sua regulação in vivo e relevância fisiológica durante o desenvolvimento e a vida adulta na função do testículo e epidídimo, tecidos responsáveis pela produção e maturação de espermatozoides, respectivamente, também foram discutidos. Arq Bras Endocrinol Metab. 2009;53(8):934-45 Descritores Receptor de androgênio; trato reprodutor masculino; testículo; epidídimo

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“…Their epithelial cells have androgen receptors and castration induces apoptotic changes (Sar et al 1990;Bentvelsen et al 1995;Mata 1995). In addition, the development and proliferation of their epithelial cells depends on several growth factors, including the fibroblast growth factor family independent of androgen (Thomson and Cunha 1991).…”

Section: Discussionmentioning

confidence: 99%

Role of Androgen on Blood Flow and Capillary Structure in Rat Seminal Vesicles

Suzuki

Kashiwagi

Shibata

et al. 2004

Tohoku J. Exp. Med.

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To clarify the effect of androgen on the microcirculation in seminal vesicles of adult Wistar rats, we investigated the organ blood flow and morphological features in the capillaries after castration and subsequent testosterone supplementation. Testosterone (T) was subcutaneously injected every 12 hours after castration and its doses were set to 10 , T10 0 and T10 1 groups, respectively). Organ blood flow was measured using laser Doppler flowmetry, and the subepithelial capillaries were analyzed using transmission electron microscopy. The capillaries were morphologically classified into 3 types; oval opened (type 1), intermediate (type 2) and collapsed (type 3), and their luminal areas were measured using a computed image analyzer. The organ blood flow was significantly reduced from 36.3±5.1 to 21.9±2.7 ml min −1 /100 g tissue, and the luminal area of the capillaries was significantly reduced from 9.02±1.28 to 4.85±0.82 μ m 2 with the shift of the type 1 and type 2 to type 3 after castration. The reduction of the luminal area and the blood flow reduction, and shift of the capillary type were significantly protected by gradated testosterone supplementation. These results indicate that the maintenance of the blood flow and morphological profiles in capillaries depend on androgen-supplementation levels in seminal vesicles. seminal vesicles; blood flow; capillary; transmission electron microscopy

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Developmental pattern and regulation by androgens of androgen receptor expression in the urogenital tract of the rat

Cited by 93 publications

References 20 publications

Effects of Flutamide on Sex Maturation and Behavior of Offspring Born to Female Rats Treated During Late Pregnancy

Effects of Flutamide on Sex Maturation and Behavior of Offspring Born to Female Rats Treated During Late Pregnancy

Androgens and the male reproductive tract: an overview of classical roles and current perspectives

Role of Androgen on Blood Flow and Capillary Structure in Rat Seminal Vesicles

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