Expression of renin in coagulating glands is regulated by testosterone

Kon, Yasuhiro; Endoh, Daiji; Murakami, Kazuo; Yamashita, Tadashi; Watanabe, Tomomasa; Hashimoto, Yoshiharu; Sugimura, Makoto

doi:10.1002/ar.1092410403

Cited by 16 publications

(29 citation statements)

References 39 publications

(38 reference statements)

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“…25 We and others have demonstrated that renin gene expression and activity can be regulated by androgens in males. 9,26,27 Indeed, in the present study, blockade of androgen receptors with Flutamide in females induced a drastic decrease of plasma renin concentrations and activity, at least to a similar degree as in males. 9 Moreover, the kidney mRNA levels for rat and mouse renin were reduced, in correlation to lower plasma concentrations and activities.…”

Section: Discussionsupporting

confidence: 61%

Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats

et al. 2003

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Abstract-We aimed at studying the role of androgens in the development of cardiovascular pathology in hypertensive female rats. Female TGR(mREN2)27 rats harboring the mouse Ren-2 renin gene were treated with Flutamide (specific antagonist of the androgen receptor, 30 mg/kg per day) starting at 4 weeks of age. Flutamide treatment significantly attenuated the development of hypertension in female rats (systolic blood pressure: treated, 134.5Ϯ5.4 versus control, 165.4Ϯ3.8 mm Hg). Heart hypertrophy was significantly reduced by the treatment (treated, 0.37Ϯ0.008 versus control, 0.45Ϯ0.01 g/100 g body wt). Urinary albumin excretion was blunted (treated, 0.4Ϯ0.1 versus control, 23.1Ϯ7.5 mg/24 hours), collagen III mRNA was significantly decreased, and no histological characteristics of end-organ damage were observed in the kidney after treatment. Flutamide treatment significantly reduced plasma renin concentrations and rat renin mRNA in kidney but not plasma angiotensinogen levels. Plasma levels of estrogens, testosterone, and luteinizing hormone were not altered. These results demonstrate that the androgen receptor antagonist Flutamide protects against hypertension and end-organ damage not only in male but also in female TGR (mREN2) Gender differences have been observed in various hypertensive animal models, with male rats having higher blood pressure than female rats, 2-6 including the transgenic rat TGR(mREN2)27 with an overactive renin-angiotensin system (RAS). 7,8 Evidence is accumulating that androgens may play an important role in gender-associated differences in cardiovascular pathology. We have previously demonstrated that androgens contribute not only to the development of malignant hypertension but also to the associated end-organ damage in transgenic male TGR(mREN2)27 rats with overactive RAS. 9 Females produce androgens as well, which act on specific receptors. 10 Women with hyperandrogenism are considered to be at increased risk for cardiovascular disease. 11-15 Based on a prospective literature survey, it has been recently hypothesized that relative androgen excess is a key factor explaining the increased risk of cardiovascular disease in interpausal women. 16 In the present study, we hypothesized that endogenous androgens may participate in the development of hypertension and end-organ damage in female TGR(mREN2)27 rats. Androgen blockade was achieved by treatment with the antagonist Flutamide, and blood pressure (BP) as well as end-organ damage, RAS, and sex hormones were evaluated. Methods Rat StrainsFemale transgenic heterozygous rats [TGR(mREN2)27] (nϭ24 rats) were obtained from the animal facilities of the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. The rats were housed individually, synchronized to a 12-hour light-dark cycle, at ambient temperature 23Ϯ2°C. A standard rat diet (ssniff R-ZUCHT) and tap water were supplied at libitum. Study DesignAll experimental protocols were performed in accordance with the guidelines for the use of laboratory animals by the Max-Delbrück-Center for...

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Section: Discussionsupporting

confidence: 61%

Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats

et al. 2003

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“…Also, renin gene expression and activity can be regulated by androgens (26,27). Therefore, the prevention of end-organ damage by Flutamide treatment could be independent of BP levels, possibly due to the inhibiting effect on the RAS.…”

Section: Discussionmentioning

confidence: 99%

Abolition of Hypertension-Induced End-Organ Damage by Androgen Receptor Blockade in Transgenic Rats Harboring the Mouse Ren-2 Gene

Baltatu

Cayla²,

Iliescu³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. A sexual dimorphism in hypertension has been observed in both human and laboratory animal studies. The mechanisms by which male sex hormones regulate cardiovascular homeostasis are still not yet fully understood and represent the subject of this study. The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harboring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with the androgen receptor antagonist Flutamide starting at 4 wk of age. Also, an androgen receptor mutation (testicular feminization mutation [tfm]) was introduced in these rats by crossbreeding male TGR(m-REN2)27 rats with tfm rats. The resulting offspring male rats that contain the tfm mutation are insensitive to androgens.Flutamide treatment or tfm mutation produced a significant attenuation of the development of hypertension. Besides a reduction in cardiac hypertrophy, urinary albumin excretion was blunted and no histologic characteristics of end-organ damage were observed in the kidney after Flutamide treatment. Testosterone levels increased 15-fold after Flutamide treatment and 2.7-fold by the tfm mutation. Also, plasma estrogens and luteinizing and follicle-stimulating hormones were significantly increased. Plasma renin concentrations and activity but not plasma angiotensinogen were reduced. Our results indicate that androgens contribute not only to the development of hypertension, but even more importantly to end-organ damage in TGR(mREN2)27 rats.Men are predisposed to hypertension and cardiovascular diseases more than age-matched, premenopausal women (1). A sexual dimorphism in hypertension has been observed both in human and laboratory animal studies (2). The mechanisms responsible for the gender differences in BP control are not yet clear and continue to be subject of active investigation (3). Evidence is accumulating that androgens may play an important role in gender-associated differences in BP regulation. Several studies have indicated that androgens may mediate hypertension and renal injury (4 -8). However, the mechanisms by which male sex hormones regulate cardiovascular homeostasis are not yet fully understood (3) and represent the subject of this study. There are indications for an interrelation between androgens and the renin-angiotensin system (RAS) (3); therefore, we studied the consequences of androgen receptor blockade on the development of malignant hypertension in transgenic TGR(mREN2)27 rats with overactive RAS (9,10). Androgen receptor inhibition was achieved by treatment with the antagonist Flutamide or by introducing a testicular feminization mutation (tfm) mutation, and BP as well as end-organ damage and RAS and pituitary-gonadal hormones were evaluated. Materials and Methods Rat StrainsMale transgenic heterozygous rats [TGR(mREN2)27] (n ϭ 24 rats) were obtained from the animal facilities of the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. Female Long-Evans rats carrying the X-linked rece...

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“…Developmental observations provide evidences that RC cells in the CG of mice are physiologically expressed after birth, especially during the adolescent period. After castration, RC cells are not demonstrated in terminal ducts of the CG, whereas weak renin immunoreactivity is still observed in the main duct [52,53]. After testosterone administration to castrated mice, large numbers of RC cells can be detected.…”

Section: Coagulating Gland (Cg) Reninmentioning

confidence: 95%

“…Renin from the CG in mice has a yet undetermined functional role [22,46]. However, it has been emphasized that the CG renin is significant because large amounts of both mRNA and protein can be detected in this organ, as well as in JG cells in the kidney [23,[50][51][52] (Fig.…”

Section: Coagulating Gland (Cg) Reninmentioning

confidence: 99%

Comparative Study of Renin-Containing Cells. Histological Approaches.

Kon

1999

The Journal of Veterinary Medical Science

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ABSTRACT. The juxtaglomerular apparatus is known to be the functional unit of renin control. In the present review, the author will describe the comparative characteristics of renin-containing (RC) cells as well as extrarenal distribution, paying special attention to developmental and topographical approaches. The characteristic locality of RC cells suggests that the secretion of renin is performed at a site beside the adventitia or via the glomerular capillaries. Ontogenetical and phylogenetical investigations of RC cells have provided interesting findings on their morphogenesis. Analysis of the endocrine kidney after unilateral obstruction of the ureter provides some findings about the origin of RC cells and the processing of renin granules. Observation of developing adrenal renin suggests that there is important involvement of angiotensin II produced by renin synthesis in the morphogenesis of the adrenal gland in the fetal stage. Coagulating gland (CG) renin is characterized by testosterone-regulated and exocrine mechanisms. Recently, all or some of the components of the renin-angiotensin system (RAS) have been reported to be synthesized and secreted outside of classical organs or tissues. In the future, the real function of local RAS will be clarified by using gene targeting in mice.-KEY WORDS: coagulating gland, development, immunohistochemistry, kidney, renin-angiotensin system.

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Expression of renin in coagulating glands is regulated by testosterone

Abstract: It is suggested that CG renin of the mouse is expressed together with sexual maturation during development and that it depends on the testis, possibly the male sex hormone.

Cited by 16 publications

References 39 publications

Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats

Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats

Abolition of Hypertension-Induced End-Organ Damage by Androgen Receptor Blockade in Transgenic Rats Harboring the Mouse Ren-2 Gene

Comparative Study of Renin-Containing Cells. Histological Approaches.

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