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Effects of castration on specific glycoprotein secretions of the epididymis in the rabbit and hamster.

Mature male rabbits and hamsters were bilaterally castrated and their epididymides were examined, at 2, 4, 7, 9 and 14 days after operation, for the presence of several glycoproteins by using monospecific antisera and indirect immunoperoxidase labelling. In the rabbit, there was a reduction in the glycoprotein reaction product in the epithelium of the proximal caput epididymidis by 2-4 days after castration, and the staining was weak or absent by 7-9 days. Compared with controls, there was also a marked decrease in the intensity of reaction product to glycoprotein in the lumen of the proximal and distal corpus epididymidis 2-4 days after castration although spermatozoa still filled the duct in this region. Glycoprotein was present in the distal cauda epididymidis at 14 days but staining diminished as spermatozoa were cleared from the tract. In the hamster, epididymal glycoproteins were apparently less critically dependent on androgens than those in the rabbit, reaching a weak but constant level in the proximal region by 7-9 days after castration and remaining at the same intensity in the distal cauda epididymidis throughout the study. These results suggest that the secretion of specific glycoproteins by the mammalian epididymis is related to androgen levels and to sperm maturation.

Animals↗

Chronic ethanol ingestion enhances GnRH-stimulated LH responses of castrated male dogs.

Dogs were given no ethanol, 1.28 g ethanol/kg and 1.92 g ethanol/kg daily for 4 weeks immediately after castration. Plasma LH concentrations, basal and in response to 100 micrograms GnRH, were measured before and at 2 and 4 weeks after castration. Basal LH levels after castration increased significantly (P less than 0.005) within each group but were not significantly different between groups. GnRH-stimulated LH responses were similar before and at 23 weeks after castration, but at 4 weeks the dogs given 1.92 g ethanol/kg had a significantly (P less than 0.05) greater response than did the control dogs. It is concluded that daily ethanol ingestion in the amounts employed in this study does not impair hypothalamic--pituitary function in male dogs.

Animals↗

Effects of some drugs on ripening of uterine cervix in nonpregnant castrated and pregnant rats.

The stimulating effect of some drugs on the ripening of the uterine cervix in rats was studied by measuring the wet weight of the uterine cervix and by both light and electron microscopy in nonpregnant castrated and pregnant conditions. Since the light and electron microscopic findings after estrogen (E) administration to castrated rats were similar to those found in the uterine cervix of rats at the end of pregnancy, it was concluded that E (E2 greater than or equal to E3 greater than or equal to E1) plays a major role in the ripening mechanism. It was also found that DHA-S, progesterone and relaxin had stimulating effects on cervical ripening. Oxytocin and PG (PGE2 greater than PGF2 alpha) showed the ripening activity only in pregnant condition. Moreover, oxytocin, PGE2 and PGF2 alpha potentiated the estrogen action. The effects on the increase in wet weight of the uterine cervix and microscopic findings due to DHA-S were different from E in castrated rats. It is therefore postulated that the effect of DHA-S might be mainly due to the secondary increase in E converted from DHA-S in the ovary and, in addition, to a direct effect of this medicament on the uterine cervix. There was essentially no difference in ultrastructure between the cervix of control (nonpregnant, castrated or pregnant) rats and that of rats treated with HCG, isoxsuprine hydrochloride, dihydroergotoxine, diazepam or n-butylscopolammonium bromide.

Animals↗

Effect of sex hormones on the tissue localization of nuclear estrogen receptor positively stained cells in the seminal vesicle of immature castrated rats.

We studied the changes in the tissue localization of nuclear estrogen receptor (ER) positively stained cells in the seminal vesicle of immature castrated rats under various environmental conditions of sex hormones by immunohistochemical methods. In castrated rats of 6 weeks of age, the percentage of nuclear ER positively stained cells showed remarkable increase in the periglandular stroma region, but not in the epithelium and the peripheral stroma region. Estrogen administration to castrated rats dramatically increased the percentage of nuclear ER positively stained cells in both the epithelium and the peripheral stroma region, whereas cessation of estrogen treatment caused a significant percentile decrease. These results suggest that the nuclear ER expression in both the epithelial cells and the peripheral stromal cells seems to respond to estrogen. The concomitant treatment of estradiol-17 beta (E2) with 5 alpha-dihydrotestosterone (DHT) completely inhibited these E2 mediated ER expression in the epithelium and the stroma. This result suggests that ER works only when E2 is given in the absence of DHT in the seminal vesicle of immature castrated rats.

Animals↗

Effects of neonatal adrenalectomy and castration on hormonal changes in pubertal bulls.

Plasma samples from intact, adrenalectomized, adrenalectomized and castrated and castrated bulls were assayed for LH, testosterone, androstenedione and oestradiol-17 beta from birth to 26 weeks of age. The adrenalectomized bulls, unlike the intact bulls, failed to show a rise in androstenedione at 14.5 weeks of age or a rise in testosterone at 20 weeks of age. Testosterone levels in the castrated animals remained below 0.4 ng/ml whereas androstenedione reached levels similar to those in intact bulls by 26 weeks of age. In all animals the concentration of oestradiol-17 beta in plasma remained below 25 pg/ml, although intact bulls had the highest levels. Levels of LH rose after castration but not after adrenalectomy. These data show that in bull calves absence of the adrenal glands during prepuberty delays the rise in pubertal testosterone by at least 10 weeks.

Adrenalectomy↗

Changes in follicle-stimulating hormone, luteinizing hormone, prolactin, oestradiol and progesterone concentrations in the sera of anovulatory androgenized female and castrated male parabiotic rats of the Fischer-344 strain.

The serum concentrations of FSH, LH and prolactin, as well as oestradiol and progesterone, were measured by immunoassays at various intervals up to 35 weeks after parabiotic union of an anovulatory androgenized female and a castrated male rat of the Fischer-344 strain. Modest increases in FSH (28%) and larger increases in LH (128%), compared to levels found in single adult animals, produced large increases in follicular growth, ovarian weight and oestrogen production in the female partners; thecal and interstitial elements of the ovaries were not heavily stimulated. Prolactin concentrations in the sera increased to exceedingly high levels and massive pituitary tumours were produced in all of the female partners. Development of cystic follicles with loss of granulosa-cell layers and the formation of early stages of granulosa-cell tumours progressed with time in union. Serum LH levels were as high in parabiotic as in single castrated male rats within 2 weeks, but concentrations of FSH remained much below those of the single animals until 27 weeks after castration. The results are consistent with the view that the ovaries of androgenized female rats of the Fischer strain produce some factor which prevents the post-castration rise in FSH of parabiotic male partners.

Animals↗

Behavioural action of androgen in the dove: effects of long-term castration on response specificity and brain aromatization.

Differences in the effectiveness of oestradiol-17 beta and testosterone on male courtship and vocal behaviour were examined in long-term castrated doves. Nest-orientated behaviour was restored by intramuscular injection of oestradiol-17 beta. Testosterone was effective in restoring aggressive courtship and vocal behaviour, but not for the nest-orientated behaviour. The effects of these hormones were separable, therefore, under conditions of prolonged androgen deficit, suggesting differences in their specificity of action. In-vitro assay of brain enzyme activity indicated that aromatization of testosterone to oestradiol-17 beta occurred in the preoptic area of long-term castrated doves. Preoptic aromatase activity of long- and short-term castrated doves did not differ. The ineffectiveness of testosterone in restoring nest-orientated behaviour in long-term castrated doves did not appear, therefore, to be due to a difference between the groups in the basal rate of testosterone aromatization in the preoptic area.

Animals↗

Secretion of follicle-stimulating hormone and luteinizing hormone in castrated golden hamsters during exposure to various photoperiods and to natural daylengths.

Golden hamsters were castrated and either maintained under short days of 9 h light and 15 h darkness (9L : 15D) or transferred to 12L : 12D, 13L : 11D or 16L : 8D. Plasma concentrations of FSH and LH remained low under 9L : 15D and 12L : 12D for 6-8 weeks but rose markedly within 4 weeks under 13L : 11D and 16L : 8D, suggesting a more abrupt transition between non-stimulatory and maximally stimulatory photoperiods than found in Japanese quail. Intact and castrated hamsters were exposed to natural photoperiods at a latitude of 51 degrees 27' N (Bristol) for 12 months. In the intact animals plasma FSH and LH levels and the size of the testes decreased as the daylength shortened from 12.5 to 10.5 h during autumn. This was followed by a rise in FSH output in mid-winter with an upward trend in LH secretion. The ensuing testicular recrudescence was complete before the spring equinox. The results emphasize that under natural conditions the primary factor regulating gonadal growth is the development of refractoriness to short days. In castrated hamsters there was no significant seasonal trend in LH output. Levels of FSH remained unchanged until a peak occurred in January, the same time that a peak was seen in intact animals before testicular recrudescence. A similar peak occurred in castrated hamsters maintained in 9L : 15D in the laboratory. This suggests that even in the absence of gonadal steroid negative feedback, hypothalamo-pituitary activity changes during the photorefractory period.

Animals↗

Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozocin-induced diabetes. Prevention by aldose reductase inhibitors and castration.

125I-labeled albumin permeation (IAP) has been assessed in various tissues in spontaneously diabetic insulin-dependent female BB/W rats and in male Sprague-Dawley rats with severe or mild forms of streptozocin-induced diabetes (SS-D and MS-D, respectively). In BB/W diabetic rats and in rats with SS-D, indices of IAP were significantly increased in tissues and vessels predisposed to diabetic vascular disease in humans, including the eyes (anterior uvea, posterior uvea, and retina), sciatic nerve, aorta, kidney, and new vessels formed after induction of diabetes. No evidence of increased IAP was observed in heart, brain, testes, or skeletal muscle in BB/W or SS-D rats. In MS-D rats, indices of IAP were increased only in the kidney and in new vessels formed after the onset of diabetes. Marked tissue differences were observed in the effects of two structurally different aldose reductase inhibitors (sorbinil and tolrestat) and of castration on diabetes-induced increases in IAP and in tissue levels of polyols in SS-D rats. Both aldose reductase inhibitors and castration completely prevented diabetes-induced increases in IAP in new vessels and in sciatic nerve in BB/W and SS-D rats. Both aldose reductase inhibitors also markedly decreased IAP in the anterior uvea (approximately 85%), posterior uvea (approximately 65-75%), retina (approximately 65-70%), and kidney (approximately 70-100%); castration reduced IAP in the anterior uvea (approximately 55%), kidney (approximately 50%), and retina (approximately 30%) but had no effect on the posterior uvea. The diabetes-induced increases in IAP in the aorta were reduced only slightly (approximately 20%) by aldose reductase inhibitors and castration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

Effect of aging and castration on the changes in the levels of bone gamma-carboxyglutamic acid-containing protein in bone and serum of female rat.

Using female rats from 2 to 64 weeks old, the changes in bone gamma-carboxyglutamic acid-containing protein (BGP) levels in bone and serum were studied in relation to the changes in calcium metabolism during aging. Intestinal calcium transport, serum phosphorus level, bone origin serum alkaline phosphatase activity and serum BGP content were high in rapidly growing animals and then decreased with aging. Serum BGP content correlated well to bone origin serum alkaline phosphatase activity. Bone density, bone ash content and bone BGP content increased during aging. Bone BGP content was correlated to bone density which indicates the level of bone calcification. Moreover, the effect of castration on calcium metabolism and bone and serum BGP contents were observed in young (10 weeks old) and aged (40 weeks old) female rat at 12 and 24 weeks after operation. Intestinal calcium transport in ovariectomized rat was significantly lower than in sham operated rat. Serum phosphorus level and serum BGP content were increased in castrated female rat. However, serum calcium level and bone origin serum alkaline phosphatase activity did not show a significant change in castrated female rat. Bone density was significantly decreased in aged rat at 24 weeks after operation. During aging or castration, serum BGP content changed more than bone BGP content. The determination of change in serum BGP levels in various disorders of calcium metabolism would be very informative in future study.

1-Carboxyglutamic Acid↗

Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models.

Although insulin-like growth factor binding protein-5 (IGFBP-5) has been shown to be implicated in prostate cancer progression, the functional role of IGFBP-5 in progression to androgen-independence remains largely undefined. Here, we demonstrate substantial up-regulation of IGFBP-5 during castration-induced regression and androgen-independent (AI) progression in the mouse androgen-dependent (AD) Shionogi tumor model. To analyze the functional significance of these changes in IGFBP-5, human AD LNCaP prostate cancer cells were stably transfected with IGFBP-5 gene, and IGFBP-5-overexpressing LNCaP tumors progressed significantly faster to androgen independence after castration compared with controls. Antisense mouse IGFBP-5 oligodeoxynucleotides (ODNs) were then designed that reduced IGFBP-5 expression in Shionogi tumor cells in vitro in a dose-dependent and sequence-specific manner. Growth of Shionogi tumor cells was inhibited by antisense IGFBP-5 ODN treatment in a time- and dose-dependent manner, which could be reversed by exogenous IGF-I. However, antisense IGFBP-5 ODN treatment had no additive inhibitory effect on Shionogi tumor cell growth when IGF-I activity was neutralized by anti-IGF-I antibody. Antisense IGFBP-5 ODN treatment resulted in decreased mitogen-activated protein kinase activity and number of cells in the S + G2-M phases of the cell cycle that directly correlated with reduced proliferation rate of Shionogi tumor cells. Systemic administration of antisense IGFBP-5 ODN in mice bearing Shionogi tumors after castration significantly delayed time to progression to androgen independence and inhibited growth of AI recurrent tumors. These findings suggest that up-regulation of IGFBP-5 after castration serves to enhance IGF bioactivity and raise the possibility that the response of prostate cancer to androgen withdrawal can be enhanced by strategies, such as antisense IGFBP-5 ODN therapy, that target IGF signal transduction.

Androgens↗

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Androgen Antagonists↗

[The state of heat exchange and thermoregulation in animals castrated at different ages].

A change of the indices of thermal metabolism and of thermoregulation in male rats with reduction of the gonad function in the aging animals and following castration at different age was studied by means of calorimetric unit permitting to record total heat emission, "direct" heat production, and also the body temperature of the animals in experiments of any duration. Functional "cold" test was used to assess the adaptive possibilities of thermoregulation. Old unoperated males showed a reduction of background values of heat exchange, diminished increase of the indices of heat production and lesser rate of body temperature restoration following the "cold" test. Castration of old animals produced no effect on already changed indices of heat exchange. But in the young castrated males there was a reduction of the initial values of heat emission and of heat production, and a change of thermoregulation reaction in response to chilling. Administration of testosterone-propionate to young castrated animals led to a partial restoration of the indices under study.

Aging↗

A new castration technic in the guinea pig.

A castration technic was perfected for removing seminiferous tubules and Leydig cells from the tunica albuginea, leaving the epididymis and its nerve and vascular supplies intact. There was a significant decrease in seminal vesicle weight in 15 guinea pigs castrated by this new procedure, indicating that the testicular androgen source was removed during castration. Spermatozoa remained motile in the ductus deferens of 18 animals that had been castrated for periods ranging from 7-70 da. The longevity of spermatozoa in the excurrent ducts was attributed to minimal trauma and damage to the ducts and their vascular and nvere supplies using this new technic.

Animals↗

Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of "compensatory" muscle hypertrophy in the rat.

1. Maximum compensatory hypertrophy of the soleus and plantaris muscle in male rats is attained seven days after tenotomy of the gastrocnemius muscle (39% and 9% respectively). When tenotomy of the gastrocnemius was performed seven days ater hypophysectomy, hypertrophy in these two muscles was aproximately half that found in control animals. 2. After 81-day castration of young male rats the weight of the saleus and plantaris was reduced and hypertrophy following tenotomy of the gastrocneumius muscle did not develop. 3. Chronically castrated rats received testosterone two weeks prior to tenotomy of the gastrocnemius and a week during the muscle hypertrophy phase. Hypertrophy of the soleus in castrated rats which had received testosterone seven days after tenotomy of the gastrocnemius was 25% as compared with muscles of castrated animals. The corresponding value in the plantaris muscle was 10%. 4. These results indicate that even calf muscles of the rat, namely the soleus and plantaris muscles, are significantly affected by testosterone under these conditions, although it is not, as yet, clear whether its action is direct or indirect.

Animals↗

[Experimental sialadenitis in castrated rats administered estrogens].

Salivary glands are dependent on sexual hormones. The aim of the present work is to study the behavior of inflammatory response induced in animals that were castrated and injected with estrogens. Male adult wistar castrated rats (60-90 days) were used. A phlogogen pellet (zinc-oxide-turpentine essence) was placed between their sublingual and submaxillary glands and they were daily injected with 5 units of estrogen. The rats were killed after 8 and 12 days of treatment; submandibular pack was weighed, dissected and fixed in phormol Ph7 for its morphohistochemical study. Phlogogen pellet breaks out an acute inflammatory response that appears attenuated in castrated animals. Such character is enhanced when estrogens are used, disappearing ductal ectasis, becoming evident a granulation tissue of strange body in phagocytic activity and in contact with the pellet. As a consequence its follows that estrogen administration in castrated animals attenuates acute inflammatory response broken out by phlogogen pellet, determining characters with tendency to chronicity and giant cells differentiation of strange body.

Animals↗

[A comparison of suturing and non-suturing of scrotal wounds following castration in stallions].

It was found that wound infections may be considerably reduced when castration is carried out under strictly aseptic conditions. In this clinical review, healing of the wound following castration with and without closure of the scrotal wounds is compared. All castrations were performed under similar aseptic conditions, general anaesthesia having been produced in the recumbent stallion. The results do not show that there is a significant difference in the appearance of wound infections in scrotal wounds which are closed and those which are left completely open. On the basis of both papers and the present review it is concluded that wound healing is more affected by the (a)septic conditions under which surgery is performed rather than by the actual method of castration.

Animals↗

[Effects of castration and estradiol dipropionate on carcinogenesis of methylcholanthrene-induced gallbladder cancer in male hamsters].

The study used 8 groups of 8-10 week-old male hamsters. Beeswax pellets containing 5 mg of 20-methylcholanthrene (group 4) or 2 mg (group 5) were injected into the gallbladder. In group 6, the latter treatment was supplemented with castration and subcutaneous injection of 40 micrograms of estradiol dipropionate (EP) once a week. Other experimental exposures included: sham operation (group 2), beeswax pellet injection into the gallbladder (group 3), beeswax pellet injection + castration + EP (group 7) and castration + EP (group 8) with the animals is group 1 being in control. The gallbladder tumor development frequency in groups 4, 5 and 6 was 58.3; 39.3 and 77.8%, respectively. The difference between the data on group 5 and 6 proved significant. The study on cumulative likelihood of tumor development showed a significant increase in tumor frequency in group 6 as compared with group 4 and 5. A strong stimulating effect of castration and EP treatment on tumorigenesis in the gallbladder was demonstrated.

Animals↗