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Histomorphometric study of the inferior urinary tract of adult female rats during the interval between castration and hormonal replacement.

OBJECTIVE: To evaluate the epithelial thickness, number of vessels, amount of collagen and muscular fibers of the bladder and urethra of castrated adult female rats during the time between castration and the beginning of the administration of synthetic conjugated estrogen. METHOD: 118 adult female rats were divided into four groups: Group I (n = 30): noncastrated female rats; group II (n = 30): female rats treated with synthetic conjugated estrogen in the dose of 50 microg/animal/day for 28 days, beginning immediately after castration; group III (n = 28): female rats treated with synthetic conjugated estrogen, 50 microg/animal/day for 28 days, beginning 30 days after castration: group IV (n = 30): female rats sacrificed after 30 days of castration. The histology of the bladder wall and the medium-third of the urethra wall were evaluated after flushing with hematoxylin-eosin and picrosirius for morphometric analysis. RESULTS: It was verified that the epithelial thickness in groups II and III were similar whereas in groups I, II and III the thickness of the bladder and also the urethra were larger than in group IV. Concerning the bladder groups I and II were similar. In group I the urethra was superior than in groups II and III. In relation to the number of vessels and muscular fibers, groups I, II and III were similar to each other and superior to group IV in the bladder and urethra. The amount of collagen was similar in groups I, II and III and inferior in group IV in the bladder and in the urethra. CONCLUSION: Independent of the time of estrogen administration (immediate or within 30 days) after castration, the thickness of the epithelium, the number of vessels, amount of collagen and muscular fibers were similar. The female rats with estrogen replacement presented significantly larger thickness of the epithelium, number of vessels and muscular fibers, and a smaller amount of collagen in the bladder and urethra in relation to the castrated group. Finally, estrogen therapy (immediate and 30 days after castration) reverted the effects of the estrogen deficiency in the vessels, collagen and muscular fibers, the bladder and of the urethra when compared to the group of castrated female rats, thus becoming similar to noncastrated animals.

Animals↗

An investigation of the requirement for increased LH secretion during the compensatory response in androgen secretion after unilateral castration of the adult rat.

The endocrine mechanisms underlying the response to unilateral castration were examined by determining systemic androgen and luteinizing hormone (LH) concentrations, as well as testicular vein androgen at 3, 6, 12, and 24 hours after sham surgery and castration. Systemic androgen was significantly depressed 3 hours after unilateral castration, but had recovered to concentrations observed in sham operated rats at 6, 12, and 24 hours. The recovery of serum androgen after castration was apparently due to increased testicular secretion of androgen, seen as a significant increase in testicular vein androgen. Systemic concentrations of bioactive and immunoactive LH were significantly increased only at 6 hours after castration. The authors next examined whether the increase in LH was necessary for the compensatory secretion of androgen seen after castration. This was accomplished by examining the response to castration when circulating LH was prevented from changing by suppressing endogenous LH secretion with subcutaneous steroid implants and maintaining circulating LH with subcutaneous osmotic pumps containing ovine LH. The compensatory increase in testicular vein androgen was observed 1 and 7 days after castration in rats bearing sham implants. When circulating LH was prevented from changing by using the combination of steroids and LH, however, compensatory secretion of androgen did not occur 1 and 7 days after castration.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

[Effect of analgesics on the castration of male piglets].

According to the current German animal welfare law, male piglets may be surgical castrated without anaesthesia up to four weeks of life. This surgical procedure is painful during and also after the operation, for newborn animals as well as for adults. This study was aimed to investigate the impact of preoperative application of analgesics (Meloxicam) on the postoperative castration - pain of four to six days old male piglets. In this investigation all animals were randomly distributed in three groups:the first one was only immobilized but had no surgery, the second one was castrated without analgesics, and the third group was castrated after application of Meloxicam. Blood samples were taken immediately before immobilization, castration or application of the analgesic as well as one, four and 28 hours afterwards to determine Cortisol-concentration in the blood serum and, via this stress-marker, to indirectly evaluate the postoperative und possible intraoperative castration-pain. As a result all piglets castrated without preoperative application of Meloxicam showed significantly increased Cortisol-concentration one and four hours after castration. In contrast, piglets castrated with analgesics resulted in no significant increase during the entire experiment.

Analgesics, Non-Narcotic↗

Effects of castration before and after treatment with N-bis (2-hydroxypropyl)-nitrosamine (DHPN) on the development of thyroid tumors in rats treated with DHPN followed by phenobarbital.

The effect of castration on the development of thyroid tumors was studied histologically and biochemically in Wistar rats given a single ip injection of 210 mg of N-bis (2-hydroxypropyl)-nitrosamine (DHPN) followed by phenobarbital (Pb). Castration was performed one week after, or one week before the injection of DHPN. The injection of DHPN was given at the end of the first week, and the rats were fed 500 ppm Pb in the basal diet for 38 weeks from week 3 to week 40. The incidence of thyroid adenomas and cancers was 20% (4/20) and 10% (2/20) in rats treated with DHPN alone. It was 75% (15/20) and 40% (8/20) in rats treated with DHPN and Pb; 30% (6/20) and 15% (3/20) in rats treated with DHPN and Pb, and castrated after DHPN; 20% (4/20) and 0% in rats treated with DHPN and Pb, and castrated before DHPN and Pb; and 0% and 0% in rats castrated either before or after receiving DHPN. Castration thus inhibited the development of thyroid tumor in rats treated with DHPN. The inhibition of tumor development in rats treated with DHPN and Pb, and castrated before receiving DHPN, was greater than in the rats castrated after receiving DHPN. Castration inhibited the secretion of TSH in rats treated with DHPN and Pb.

Animals↗

Disparate effects of castration on renal structure and function in the streptozotocin diabetic rat.

Diabetic children are protected from the complications of diabetes until puberty, suggesting the involvement of a hormonal mechanism. In order to investigate the contribution of sex steroids to the development of diabetic nephropathy, castrated Wistar-Kyoto rats were made diabetic with streptozotocin and compared with intact diabetic rats. In intact rats, 32 weeks of diabetes resulted in hyperfiltration (p = 0.0001) and a marked increase in albuminuria (control, 1.3 x/divided by 1.3 vs diabetes intact, 11.8 x/divided by 1.3 mg/day, p < 0.001). Concomitant structural changes included glomerular basement membrane thickening (diabetes, 199.2 +/- 7.9 vs control, 175.9 +/- 3.9 nm, p = 0.02) and increased mesangial volume (diabetes, 194 +/- 14 vs control, 129 +/- 20 microns 3, p = 0.02). Although castration resulted in blood pressure lowering of 12 mmHg (p = 0.0003), albuminuria increased to the same extent in intact and castrated diabetic rats (castrated diabetic 10.5 x/divided by 1.3 mg/day). Glomerular filtration rate was lower in castrated rats than in intact rats prior to induction of diabetes, but increased similarly with induction of diabetes. Castrated diabetic rats had increased mesangial volume (castrated diabetic, 213 +/- 20 microns 3), but glomerular basement membrane thickness was lower than in intact diabetic rats (castrated diabetic, 179.5 +/- 4.5 nm). Thus, there is a dissociation between basement membrane thickening and albuminuria in this model of diabetic kidney disease. The mechanism of action of castration on glomerular function and structure remains to be elucidated but may relate to indirect effects such as reduction of blood pressure or renal polyol accumulation or a direct effect of sex steroids.

Albuminuria↗

Castration attenuates proteinuria and glomerular injury in unilaterally nephrectomized male Sprague-Dawley rats.

BACKGROUND: To clarify the pathogenesis of focal and segmental glomerulosclerosis, we investigated the effect of castration on the development of proteinuria and glomerulosclerosis in unilaterally nephrectomized male Sprague-Dawley (SD) rats. EXPERIMENTAL DESIGN: At 5 weeks of age, group 3 was castrated, whereas groups 1 and 2 were sham-operated. At 6 weeks of age, groups 2 and 3 received unilateral right nephrectomy and group 1 received sham-operation. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, blood urea nitrogen and serum creatinine were checked every 2 months from 2 through 12 months after right nephrectomy. Control group 1, Nx (nephrectomized) group 2 and castrated (nephrectomized + castrated) group 3 underwent morphologic study 6 months after nephrectomy. In an additional experiment, control group 4, Nx group 5, and castrated group 6 were followed for an additional 6 months and used for morphologic study. RESULTS: Growth was significantly stunted in the castrated rats as compared with control and Nx rats. Nx rats became proteinuric with age. Castration significantly reduced the proteinuria after 2 months of nephrectomy throughout the experiment. The proteinuria in castrated rats tended to decrease as compared with the controls. The glomerulosclerosis index was significantly higher in Nx rats than in either the controls or the castrated rats. The three groups showed no significant differences in blood pressure, plasma renin, activity and plasma aldosterone concentration. CONCLUSIONS: These observations suggest that sex hormones may contribute to the development of proteinuria and glomerulosclerosis in unilaterally nephrectomized male SD rats.

Animals↗

[The estrogen-induced changes of estrogen receptor in seminal vesicle of immature castrated rat].

We have already reported that estrogen treatment given to immature castrated rats caused proliferative changes in both collagen and smooth muscle in the seminal vesicles of immature rats detected by light microscopy. Herein, we studied the estrogen-induced changes in estrogen receptor (ER) in the seminal vesicles of immature castrated rats by means of enzyme immunoassay, an immunohistochemical method and RT-PCR, to clarify the mechanism of estrogen induced proliferation of collagen and smooth muscle. Immature rats (3 weeks old) were castrated and left untreated for 3 weeks and then injected subcutaneously with estradiol-17 beta (E2-17 beta, 5 micrograms/day) for 7 days before they were killed. The nuclear ER content per gland, mg tissue and mg protein in the seminal vesicles of castrated rats increased markedly compared with those of non-treated rats. Castration also enhanced ERmRNA expression. The immunohistochemical analysis demonstrated the obvious tissue distribution by which the nuclear ER positive cells were densely distributed in the periglandular stroma. The nuclear ER contents per gland, mg tissue and mg protein in the seminal vesicles of estrogen-treated castrated rats were greater than those in castrated rats. Estrogen treatment further enhanced ERmRNA expression in the castrated rats. The immunohistochemical studies demonstrated that the nuclear ER positive cells appeared among the glandular epithelial cells, basal cells and the peripheral stromal cells, in addition to the periglandular stromal cells. These findings suggest that ER is related to the estrogen induced proliferation of collagen and smooth muscle in the seminal vesicles of immature castrated rats.

Animals↗

Intercellular communication within the rat anterior pituitary gland: V. Changes in cell-to-cell communications as a function of the timing of castration in male rats.

Cell-to-cell communication by gap junctions was investigated in the male rat anterior pituitary gland following several experimental regimens involving castration. The regimens included the following animals: (1) Group 1, castrated at 10-day intervals from day 10 to 50 and sacrificed at 60 days of age; (2) Group 2, castrated every 10 days from days 10 to 50 and sacrificed 50 days after castration; (3) Group 3, castrated at 5 days of age and sacrificed every 10 days from day 10 to 60; or (4) Group 4, remained intact and sacrificed every 10 days from days 10 to 60. In all of the castrated animals, numerous so-called castration cells were scattered throughout the pars distalis of the pituitary gland, with occasional "signet ring cells" being observed. In Groups 1 and 2, the pattern of gap junction development and their number was no different from the intact control (Group 4). In contrast, the number of gap junctions in the animals castrated on day 5 remained very small even into adulthood. These data demonstrate that gonadal steroids are important in the initial development of gap junctions within the pituitary gland but are not necessary to sustain their presence once an animal becomes an adult.

Animals↗

Freeze-fracture, ultrastructural and autoradiographic analysis of the ventral prostate glands in castrated mice.

Ultrastructure of the ventral prostate glands was studied in mice castrated for 1 through 60 days and for 11 and 17 months and in age-matched normals. We have described freeze-fracture and ultrastructural characteristics of acinar epithelial cells in addition to the patterns of thymidine incorporation in the cells of castrates and normal animals. Our study has shown a biphasic pattern of prostatic involution in the long-term castrated mice. In castrates the initial atrophy of prostate glands occurred by sloughing of the apical portions of columnar cells, autophagia of the cytoplasmic organelles as well as by occasional sloughing of the individual cells into the acinar lumen. Concurrent with the initial atrophy, the glands and stroma were infiltrated by neutrophils and lymphocytes. The cell loss by sloughing and leucocyte infiltration of glands became infrequent in 7- to 21-day castrates. However, the cell loss by sloughing increased secondarily in mice castrated for 21 to 37 days along with the increased leucocyte infiltration of the glands. The cell loss became minimal in castrates of 60 days and beyond. Our evidence suggests that the cell loss by sloughing was an active process in the involution of prostate glands which also showed differential sensitivity to castration stimuli in mice.

Animals↗

Sexual behavior of castrated sex offenders.

Data are reported on the sexual behavior of 39 released sex offenders who agreed voluntarily to surgical castration while imprisoned in West Germany. Findings indicated that frequency of coitus, masturbation, and sexual thoughts are seen as strongly reduced after castration. Sexual desire and sexual arousability are perceived by the subjects as having been considerably impaired by castration. In comparison with other studies, however, it was shown that male sexual capacity was not extinguished soon after castration. Particularly noteworthy is that 11 of 35 castrates (31%) stated they were still able to engage in sexual intercourse. Rapists proved to be sexually more active after castration than homosexuals or pedophiliacs. There seems to be a strong effect on sexual behavior only if castration is performed on males between the age of 46 and 59 years. In general, the findings do not justify recommending surgical castration as a reliable treatment for incarcerated sex offenders.

Adult↗

The development of photorefractoriness in castrated willow ptarmigan (Lagopus lagopus lagopus).

Changes in plasma LH levels were observed in castrated willow ptarmigan exposed to different lighting patterns to determine whether they become photorefractory. LH levels did not increase in long-term castrated birds exposed to a natural (70 degrees N) increase in daylength and did not fall abruptly in June when intact birds become photorefractory. Plasma LH levels in naturally photostimulated, long-term castrates fell gradually during the summer and fall. Plasma LH levels increased steeply when these birds were transferred in winter from short days to continuous light. Thereafter the levels fell indicating that the birds became photorefractory. In a further experiment, photosensitive male willow ptarmigan were castrated 3 or 6 weeks after transfer from short days to continuous light. The postcastration increase in plasma LH levels was significantly greater in birds castrated after 3 weeks than in those castrated after 6 weeks of photostimulation. In both groups of castrates, LH levels began to fall when LH levels decreased in intact controls, indicating the development of photorefractoriness. These findings confirm that the development of photorefractoriness is progressive rather than abrupt and that it may be accelerated in castrated birds under natural increases in daylength but not after acute transfer from short days to continuous light. These observations support the view that the development of photorefractoriness in willow ptarmigan involves an interaction between the gonads and the neuroendocrine or circadian system. They are not entirely consistent with the simple concept that photorefractoriness is caused by a decrease in the sensitivity of the hypothalamus to inhibitory steroid feedback.

Animals↗

Effect of testosterone on the rate of myofibrillar protein breakdown in castrated and adrenalectomized male rats measured by the urinary excretion of 3-methylhistidine.

Urinary output in N tau-methylhistidine (3-MeHis) was used to evaluate changes in myofibrillar protein breakdown rate in the skeletal muscles of castrated and adrenalectomized-castrated young male rats, and the response of breakdown to testosterone and corticosterone replacement. The castrated rats grew less well than intact control rats and excreted significantly less 3-MeHis. Administration of low and high doses of testosterone restored the weight of the levator ani of the castrated animals but failed to affect growth rate or 3-MeHis output. Although this might suggest that testosterone has an indirect effect on muscle turnover through changes in growth rate, this parallelism was not confirmed by studies on adrenalectomized-castrated rats. Adrenalectomy of castrated rats caused a further reduction in growth rate and in output of 3-MeHis, but administration of testosterone now reduced 3-MeHis output still further while stimulating growth. Treatment of the adrenalectomized-castrated rats with low doses of corticosterone increased growth modestly, while depressing 3-MeHis output, and again output of this metabolite was further reduced when testosterone was added to the treatment, although growth rate was unaffected. Finally, large doses of testosterone given to adrenalectomized-castrated rats receiving excessive amounts of corticosterone did not prevent the growth failure or the increased output of 3-MeHis due to the corticosteroid, though it appeared to reduce the magnitude of the response to corticosterone alone. It is concluded that the effects of testosterone on growth and on 3-MeHis output are not necessarily associated and that the functional status of the adrenal cortex modifies the response of myofibrillar breakdown rate to testosterone treatment.

Adrenalectomy↗

Sexual difference in the incidence of diabetes mellitus in Otsuka-Long-Evans-Tokushima-Fatty rats: effects of castration and sex hormone replacement on its incidence.

The incidence of non-insulin-dependent diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]) has been shown to be much higher in males than in females. To evaluate the role of sex hormones in the development of diabetes in this model, we performed biochemical and morphological studies on the effects of castration and sex hormones on the development of non-insulin-dependent diabetes mellitus in these rats. The rats were randomly assigned to six groups of 10 rats each, three groups of males and three of females. Two of the male groups and two of the female groups were castrated at 5 weeks of age, and the third male and female groups received sham operations. From 9 to 30 weeks of age, one group of castrated males received testosterone enanthate (1 mg-wk-1) and one group of castrated females received estradiol valerate (1 mg.wk-1). The other castrated groups received an equal volume of vehicle only. At 30 weeks of age, the cumulative incidences of diabetes mellitus in the sham-operated male and female rats were 100% and 0%, respectively. Orchiectomy reduced the incidence of diabetes to 20%, whereas ovariectomy increased it to 30%. Administration of sex hormones restored the incidence to 89% in males and 0% in females. In vivo insulin-stimulated glucose uptake as measured with a euglycemic clamp was reduced in sham-operated males, castrated males with hormone replacement (HR), and castrated females without HR as compared with sham-operated females and castrated females with HR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens.

The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (approximately = 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 (approximately 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity.

Animals↗

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Aged↗

The effects of neonatal castration on the subsequent behavioural response to centrally administered arginine vasopressin and the expression of V1a receptors in adult male prairie voles.

Centrally administered arginine vasopressin induces the formation of partner preferences in male prairie voles (Microtus ochrogaster). The expression of many vasopressin-regulated behaviours is testosterone dependent. In this study, we tested the hypothesis that early exposure to gonadal steroids are necessary to establish the typical response of adult male prairie voles to exogenous vasopressin, predicting that adult males which were castrated neonatally would not form partner preferences in response to centrally administered vasopressin. We also examined the effect of neonatal castration on the expression of vasopressin (V1a) receptors. Voles were castrated on the day of birth (NEOCAST), sham-castrated on the day of birth (NEOSHAM) or castrated as adults (ADULTCAST). With the exception of one group of neonatal sham males (NEOSHAM CON), which served as a control for the effects of vasopressin, as adults, all males received a 1- micro l intracerebroventricular injection of vasopressin (100 ng) in artificial cerebrospinal fluid. In addition, 2 weeks before testing, one group of neonatally castrated males received an implant of testosterone propionate (NEOCAST + TP). Between 60 and 90 days of age, an internal cannula was placed in the lateral cerebral ventricle and, 24 h later, males were injected with vasopressin. Subsequently, after an additional 15 min, males were cohabitated with a female 'partner' for 1 h. Immediately following cohabitation, males were placed in a Y-shaped partner preference test apparatus for 3 h, in which the male had access to the 'partner' and a novel female, 'stranger.' Time spent with the partner versus the stranger was compared within and between treatments. The results were found to support our hypothesis as the NEOSHAM and ADULTCAST males formed partner preferences, spending more time with the partner, and they spent significantly more time with their partner than did NEOSHAM CON, NEOCAST or NEOCAST + TP males. Replacement of testosterone in neonatally castrated males did not restore partner preference formation in response to vasopressin in adult males. Finally, neonatal castration did not affect the distribution of V1a receptors.

Age Factors↗

Effects of castration and testosterone on Fel dI production by sebaceous glands of male cats: II--Morphometric assessment.

A morphometric study of cat sebaceous glands was performed to evaluate the effects of castration and testosterone treatments. Skin biopsies were taken in six cats before castration, after castration and after the testosterone injections administered after castration (total number of biopsies: 18). Ninety 8 microns thick sections of each biopsy were assessed for image analysis processing (SAMBA 2005, ALCATEL TITN). The variations in glands and cells size were evaluated on digitized microscopic images by morphometric parameters included in the SAMBA software package. An original software was developed for the analysis of the spacial gland structure. The best morphometric parameters were selected in a first step of the study, and included the nuclear surface (NS), the cell surface (CS) and the nuclear/cellular surface ratio (N/C). These three parameters were then compared in each group of samples for the six cats. It was shown that after castration the N/C (21%) significantly increased compared with prior to castration (12.6%). This 59.8% increase was mainly due to cell cytoplasm shrinking reflecting a decrease of the cell activity. The testosterone administered after castration produced a reverse effect with a N/C ratio back to normal (11.4%) and a significant cell cytoplasm and gland enlargement as shown by the three dimension constructions. This morphometric data correlated with the measurement of sebum and Fel dI productions. The negative effects of castration and the positive effects of testosterone on the sebaceous cells and glands volume favour the hypothesis that cat sebaceous cells are subject to hormonal control this is also likely to apply to the Fel dI production.

Allergens↗

Attenuating effect of castration on glomerular injury is age-dependent in unilaterally nephrectomized male Sprague-Dawley rats.

To clarify a role of sex hormones in greater susceptibility of young rats than adults to the development of focal and segmental glomerulosclerosis (FSGS), we castrated animals at different ages and investigated whether the attenuating effect of castration on FSGS is age-dependent in unilaterally nephrectomized male Sprague-Dawley (SD) rats. At 6 weeks of age, all groups received unilateral right nephrectomy (Nx) and group 2 was simultaneously castrated, while group 1 received a sham operation. Group 3 was castrated at 3 months of age, and group 4 at 6 months of age. Body weight, blood pressure, urinary protein and serum constituents were investigated every 2 months from 4 to 14 months of age. At 6 and 14 months of age, rats were studied morphologically. Castration at 6 weeks of age or at 3 months of age significantly inhibited the compensatory glomerular hypertrophy and hyperfunction with regard to the creatinine clearance as seen in Nx rats at 6 months of age and significantly reduced glomerular injury at the end of the experiment, while castration at 6 months produced neither an inhibitory effect on glomerular hypertrophy nor an attenuating effect on glomerular injury. Serum levels of growth hormone (GH) and somatomedin-C (SmC) were decreased by castration to a greater extent when castrated at younger age. These findings indicated that GH and SmC influenced by male sex hormone seem to play a more important role at younger age than in adults in exerting its effect on glomerular growth, leading somehow to glomerular injury in aging, unilaterally nephrectomized male SD rats.

Aging↗