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

Nakamura, Megumi; Ikeda, Yûji; Mine, M; Tomiyoshi, Yoshiyuki; Sakemi, Takanobu

doi:10.1159/000046118

Cited by 7 publications

(8 citation statements)

References 20 publications

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“…These results suggest that glomerular hypertrophy is probably related to increased GH levels in the estrogen-treated OLETF rats, similar to what has been observed previously in uninephrectomized Sprague-Dawley rats [29]. In addition, we have recently reported that the somatostatin analogue attenuates estrogen-induced augmentation of glomerular injury in spontaneous hypercholesterolemic female Imai rats associated with a reduction of glomerular hypertrophy [30]. On the basis of these results and findings, it is possible that glomerular hypertrophy may be responsible for renal damage [25].…”

Section: Discussionsupporting

confidence: 89%

Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Tomiyoshi¹,

Sakemi²,

Aoki³

et al. 2002

Nephron

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Aim: Non-insulin-dependent diabetic mellitus model rats, Otsuka-Long-Evans-Tokushima-Fatty (OLETF), develop diabetic nephropathy presenting with mesangial expansion leading to glomerular sclerosis and thickening of the glomerular basement membrane (GBM), especially in elderly males. The effects of sex hormones and castration on the incidence of diabetes mellitus (DM) have been studied in this strain rat. However, there have been no detailed studies on the effects of castration and sex hormone in the development of diabetic nephropa-thy. Methods: In this study we examine the effect of cas-tration or estrogen on the development of glomerular injury in OLETF rats. Thirty male OLETF rats and 10 male long-Evans Tokushima Otsuka (LETO) rats as a normal control were used. OLETF rats were divided into three groups: group 1 received sham-operation, group 2 was castrated at 6 weeks, and group 3 was administered 0.1 mg estrogen subcutaneously once a month from 6 weeks to 58 weeks of age and LETO rats were assigned to group 4. Body weight, urinary protein and fasting blood glucose, serum albumin and other serum constituents were investigated every 12 weeks from 12 weeks to 60 weeks of age. In groups 1-3, glucose tolerance test was performed at 38 weeks. Each group was studied morphologically at the end of the experiment (60 weeks of age). Results: Castration attenuated proteinuria and glomerular sclerosis accompanied by an amelioration of glucose tolerance, a decrease in mesangial expansion and an attenuation of the GBM thickening. In contrast, although estrogen equally ameliorated glucose tolerance and attenuated the mesangial expansion and the GBM thickening, estrogen failed to attenuate proteinuria and glomerulosclerosis. A significant increase in glomer-ular tuft volume, and serum levels of growth hormone, total cholesterol and triglycerides was observed in the estrogen-treated rats as compared with the castrated rats. Conclusion: Besides the mechanisms involved in the development of diabetic nephropathy, other mechanisms may be involved and contribute to the development of glomerulosclerosis in the estrogen-treated rats, leading to a difference in glomerular injury between the castrated and estrogen-treated OLETF rats.

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Section: Discussionsupporting

confidence: 89%

Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Tomiyoshi¹,

Sakemi²,

Aoki³

et al. 2002

Nephron

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“…Several other studies have also implicated a role for estrogen in the production of renal injury. In the spontaneously hypercholesterolemic Imai rat, estrogen administration aggravated the development of proteinuria and glomerular injury (17). A similar aggravating effect of estrogen has been reported in female analbuminemic rats (13) and in female obese Zucker rats (25).…”

Section: Discussionsupporting

confidence: 68%

Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats

Stier¹,

Chander²,

Rosenfeld³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Stroke-prone spontaneously hypertensive rats (SHRSP) maintained on Stroke-Prone Rodent Diet and 1% NaCl drinking water (starting at 8 wk of age) rapidly develop stroke and malignant nephrosclerosis that can be prevented, despite continued hypertension, by drugs targeting angiotensin II and aldosterone actions. This study evaluated estrogen's effects in the SHRSP model. Female SHRSP that were sham operated (SHAM), ovariectomized (OVX) at 4 wk of age, or OVX and treated with estradiol benzoate (E2,30 microg x kg-1 x wk-1) were studied. In a survival protocol, OVX rats lived significantly longer (15.1 +/- 0.3 wk) compared with SHAM (13.6 +/- 0.2 wk) or OVX+E2 rats (12.4 +/- 0.2 wk). In a protocol in which animals were matched for age, at 11.5 wk, terminal systolic blood pressure and urine protein excretion were elevated in SHAM and OVX+E2 rats compared with OVX rats; blood urea nitrogen, renal microvascular and glomerular lesions, and plasma renin concentration were elevated in OVX+E2 relative to SHAM or OVX rats. In a survival protocol using intact female SHRSP, treatment with an antiestrogen (tamoxifen, 7 mg.kg-1.wk-1) prolonged survival by >2 wk compared with controls (P < 0.01). The data indicate that estrogen promotes microangiopathy in the kidney and stroke in saline-drinking SHRSP.

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“…Further, administration of estradiol tended to mitigate the changes 6–8 . In female Imai rats, a protective or aggravative effect of estradiol on glomerulosclerosis was dependent on dose 10 which may be mediated by growth hormone 35 . Additionally, exogenous estradiol in spontaneously hypertensive rats that underwent uninephrectomy, or in female db/db mice, male Imai rats, or male Sprague-Dawley rats has been demonstrated to reduce age-related kidney disease progression 9,11–13 .…”

Section: Discussionmentioning

confidence: 91%

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

Vorland

Lachcik

Swallow

et al. 2019

Sci Rep

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Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.

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

Cited by 7 publications

References 20 publications

Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

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