Testosterone Eliminates the Attenuating Effect of Castration on the Progressive Glomerular Injury in Hypercholesterolemic Male Imai Rats

Sakemi, Takanobu; Toyoshima, Hajime; Morito, Fumitaka

doi:10.1159/000188022

Cited by 40 publications

(30 citation statements)

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“…Sex hormones may also be involved in the different evolution of renal function between males and females in response to the prolonged HPI. In support of this hypothesis, it has been shown that castration of male rats seems to have a beneficial effect on the development of glomerulosclerosis, whereas treatment with testosterone accelerates the disease (23). It has also been shown that estrogens reduce glomerulosclerosis susceptibility (19).…”

Section: Discussionmentioning

confidence: 94%

Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development

Reverte

Tapia²,

Moreno³

et al. 2011

American Journal of Physiology-Renal Physiology

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Reverte V, Tapia A, Moreno JM, Rodríguez L, Salazar F, Llinás MT, Salazar FJ. Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development. Am J Physiol Renal Physiol 301: F327-F333, 2011. First published May 25, 2011 doi:10.1152/ajprenal.00110.2011.-Cyclooxygenase 2 (COX2) is involved in regulating renal hemodynamics after renal ablation. It is also known that high protein intake (HPI) leads to a deterioration of renal function when there is preexisting renal disease and that there are important gender differences in the regulation of renal function. This study tested the hypothesis that the role of COX2 in regulating renal function and the renal hemodynamic effects elicited by HPI are enhanced when nephrogenesis is altered during renal development. It was also expected that the role of COX2 and the effects elicited by HPI are age and sex dependent. Newborn Sprague-Dawley rats were treated with an AT1 ANG II receptor antagonist during the nephrogenic period (ARAnp). Experiments were performed at 3-4 and 10 -11 mo of age. Arterial pressure was elevated (P Ͻ 0.05) at both ages and in both sexes of ARAnptreated rats. Renal COX2 expression was only elevated (P Ͻ 0.05) at 10 -11 mo of age in both sexes of ARAnp-treated rats. COX2 inhibition induced greater renal vasoconstriction in male and female hypertensive than in normotensive rats at both ages. HPI did not induce glomerular filtration rate (GFR) in the youngest hypertensive rats and in the oldest female hypertensive rats. However, the GFR decreased during HPI (0.63 Ϯ 0.07 to 0.19 Ϯ 0.05 ml/min) in the oldest male hypertensive rats. The HPI-induced increment in proteinuria was greater (P Ͻ 0.05) in male (99 Ϯ 22 mg/day) than in female (30 Ϯ 8 mg/day) hypertensive rats. These results show that COX2 plays an important role in the regulation of renal function when renal development is altered and that prolonged HPI can lead to a renal insufficiency in males but not in females with reduced nephron endowment.hypertension; proteinuria; renal function SEVERAL STUDIES HAVE PROPOSED that an alteration in nephrogenesis leads to a compensatory glomerular hypertrophy and an accelerated deterioration of renal function that are sex dependent (2,8,21,31). It has been reported that the compensatory glomerular changes that occur in male animals after subtotal ablation of renal mass are mediated by an increase in cyclooxygenase 2 (COX2) activity (7,27). However, it is unknown to what extent COX2 is involved in the regulation of renal function when nephron endowment decreases during renal development and whether this importance of COX2 is greater in males than in females. One hypothesis tested in this study is that COX2-derived metabolites are involved in the regulation of renal function when nephrogenesis is altered during the late nephrogenic period and that the role of COX2 is sex and aging dependent. A sex-dependent difference was expected since it has been reported in other mechanisms involved in the regulation of ren...

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Section: Discussionmentioning

confidence: 94%

Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development

Reverte

Tapia²,

Moreno³

et al. 2011

American Journal of Physiology-Renal Physiology

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“…This hypercholesterolemic Imai rat, derived from Sprague-Dawley rats, has a markedly elevated rate of urinary protein excretion, especially in males [1, 2, 3, 4]. Because of this higher susceptibility of male Imai rats to focal and segmental glomerulosclerosis, we previously studied the effects of sex hormones on the development of glomerular injury both in male and in female Imai rats [4, 5, 6, 7]. We found that estrogen replacement therapy does not eliminate the aggravating effect of ovariectomy on glomerular injury and rather aggravates it [8].…”

Section: Introductionmentioning

confidence: 99%

Somatostatin Analogue Attenuates Estrogen-Induced Augmentation of Glomerular Injury in Spontaneous Hypercholesterolemic Female Imai Rats

Nakamura¹,

Ikeda²,

Mine³

et al. 2001

Nephron

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Background: Aggravating effect of estrogen replacement therapy on glomerular injury associated with an elevation of growth hormone (GH) levels has been reported. Therefore, in the present study, to clarify an association between GH elevation and the aggravating effect of estrogen on glomerular injury, we investigated the effect of somatostatin, an inhibitor of GH secretion, on glomerular injury in estrogen-treated hypercholesterolemic female Imai rats. Method: Control female rats were assigned to group 1 (Cont, n = 10). Group 2 (Cont-E, n = 10) received estrogen, and groups 3 (Cont-E-LS, n = 10) and 4 (Cont-E-HS) received estrogen and either a low dose of somatostatin analogue or a high dose of somatostatin analogue. Body weight, urinary protein, serum albumin, total cholesterol, triglycerides, blood urea nitrogen and serum creatinine were investigated every 4 weeks from 10 weeks through 30 weeks of age. At 30 weeks of age, rats were studied morphologically. Results: Estrogen administration resulted in an increase in urinary protein excretion rates and serum total cholesterol levels, and aggravated glomerular injury associated with an increase in GH. In contrast, somatostatin treatment reduced both urinary protein excretion rates and total cholesterol levels and attenuated glomerular injury to levels close to those of controls associated with a reduction of GH levels. Conclusion: The results suggest that increased GH levels may contribute to an enhancing effect of estrogen administration on glomerular injury.

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“…Other in vitro studies demonstrated that estrogen inhibits procollagen type III and increases the production of collagenase (11)(12)(13). Furthermore, castration of male rats seems to have a beneficial effect on the development of glomerulosclerosis (14), whereas treatment with testosterone accelerates the disease (15). Recent studies demonstrated that glomerulosclerosis susceptibility is associated with diminished estrogen receptor expression in mesangial cells (16).…”

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confidence: 99%

Decreases in Renal Functional Reserve and Proximal Tubular Fluid Output in Conscious Oophorectomized Rats

Nielsen¹,

Flyvbjerg²,

Bruun³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Age-dependent glomerulosclerosis with reduced GFR develops earlier among men than among women. Therefore, whether female sex hormones could prevent the agedependent decrease in GFR was investigated. The kidney function in oophorectomized rats treated with placebo (OOX group), estrogen (OOXϩE 2 group), or estrogen plus progesterone (OOXϩE 2 ϩP group) for 5 mo and in sham-operated rats (sham group) was examined. The rats were 13 mo of age at the time of the investigation. They were conscious and chronically instrumented. The results demonstrated that estrogen, alone or in combination with progesterone, was without effect on the baseline GFR and effective renal plasma flow but prevented severe decreases in the renal functional reserve and fractional proximal tubular fluid output (lithium clearance technique, fractional lithium excretion), which were observed in the OOX group. The renal functional reserve (estimated by stimulation with glycine) was Ϫ223 Ϯ 151, 483 Ϯ 129, 675 Ϯ 76, and 208 Ϯ 140 l/min in the OOX, OOXϩE 2 , OOXϩE 2 ϩP, and sham groups, respectively. Fractional lithium excretion was 12.4 Ϯ 3.1, 26.8 Ϯ 2.0, 31.8 Ϯ 2.5, and 23.6 Ϯ 3.3% in the OOX, OOXϩE 2 , OOXϩE 2 ϩP, and sham groups, respectively. In conclusion, oophorectomy at the age of 8 mo did not produce a decrease in baseline GFR in female rats within a period of 5 mo. However, oophorectomy led to severe decreases in the renal functional reserve and fractional proximal tubular fluid output. Both effects were prevented with administration of estrogen. Sham-operated rats demonstrated values for renal functional reserve and fractional lithium excretion that were between those observed for the OOX group and the groups treated with sex hormones.

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Testosterone Eliminates the Attenuating Effect of Castration on the Progressive Glomerular Injury in Hypercholesterolemic Male Imai Rats

Cited by 40 publications

References 20 publications

Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development

Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development

Somatostatin Analogue Attenuates Estrogen-Induced Augmentation of Glomerular Injury in Spontaneous Hypercholesterolemic Female Imai Rats

Decreases in Renal Functional Reserve and Proximal Tubular Fluid Output in Conscious Oophorectomized Rats

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