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PubMed2006

Intermittent androgen replacement for intense hypogonadism symptoms in castrated patients.

OBJECTIVES: For locally advanced prostate cancer management, medical androgen deprivation and surgical castration are alternatives. These hormonal treatments may cause a myriad of side effects, such as osteoporosis with increased risk of fractures, anemia, behavioral changes and lack of sexual interest. We evaluated the feasibility of intermittent androgen replacement in surgically castrated patients with significant side effects. METHODS: Five patients with advanced prostate cancer, ranging from 71 to 77 years of age (mean age = 74 years), surgically castrated for at least 3 years, with important symptoms of hypoandrogenism received testosterone replacement. They were followed with PSA and testosterone measurement every other month and bone scans every 6 months. RESULTS: For the first year all patients improved significantly, none of them showed PSA increase over 10 ng/ml. There was no evidence of local recurrence or distant disease. After 18 months, only one patient (20%) had a significant PSA increase, controlled by androgen withdrawal. No side effects or metastasis were observed. CONCLUSIONS: Hormonal replacement in patients that underwent castration seems to be feasible in improving intense symptoms associated to androgen deprivation. After 18 months, no evidence of recurrence was noted. It is an experimental alternative for highly symptomatic patients, but the short follow-up and the small number of patients cannot allow for definitive conclusions and should be studied further.

Aged↗
PubMed1998

Effect of photostimulation on concentrations of plasma prolactin in castrated bantams (Gallus domesticus).

The annual breeding cycle of 'unimproved' breeds of domestic chicken, including the bantam, at temperate latitudes, is terminated by decreasing daylength in autumn and is initiated in late winter, while daylengths are still short. Observations on photoperiodic birds that terminate seasonal breeding by the development of long day photorefractoriness suggest that the photoinduced pattern of prolactin secretion is associated with the pattern of gonadal growth and regression. It was predicted that, if there is a causal relationship between photoinduced changes in prolactin secretion and gonadal function in birds then, in the bantam, the pattern of prolactin secretion observed after photostimulation would not be the same as in birds terminating breeding by the development of long day photorefractoriness. Experiments were carried out on surgically castrated bantams to avoid confounding the effects of photostimulation and the stimulatory actions of testicular hormones on prolactin secretion. Transfer of photosensitive castrated bantams from 8 to 14, 16, 18 or 20 h light/day initially stimulated prolactin release and, subsequently, after 20-30 days, concentrations of plasma prolactin progressively decreased. After 148 days of photostimulation, concentrations of plasma prolactin approached but were still higher than short day controls. Transfer of photosensitive castrated bantam cockerels from 8 to 12 h light/day stimulated a slower increase in plasma prolactin that subsequently remained higher than in other photostimulated groups. A further 4 h increase in photoperiod in the birds exposed for 148 days to 12 or 16 h light/day resulted, respectively, in a transitory increase and no increase in prolactin secretion. Recovery of photosensitivity for prolactin release was observed in the birds transferred to 18 or 20 h light/day for 148 days after treatment with 8 h light/day for 35 days. Attempts to obtain an independent hormonal correlate of the prolactin responses to photostimulation by measurement of plasma luteinizing hormone (LH) were unsuccessful. The concentration of plasma LH in castrated bantams did not change in response to a change in photoperiod. These observations show that the photoinduced pattern of prolactin release in the bantam, a species which terminates seasonal breeding in response to decreasing daylength, is the same as that in birds which terminate seasonal breeding by the development of long day photorefractoriness. It is concluded that the photoinduced pattern of prolactin secretion in birds can be dissociated from the neuroendocrine mechanisms controlling the termination of seasonal breeding.

Animals↗
PubMed1998

Effect of short photoperiods on the in vitro GnRH release by hypothalamic explants in intact and castrated male Syrian hamsters: relation to testicular regression and recrudescence.

Prolonged exposure of adult Syrian hamsters to short days decreases LH and FSH circulating levels within 2-4 weeks, then induces testicular regression. After 18 weeks of short days, the testis size and gonadotropin levels increase spontaneously. This study investigated whether these phases of photosensitivity and photorefractoriness corresponded to variations of in vitro GnRH release. Male hamsters were either kept under long days (LD 16:8) or transferred to short days (SD 6:18) and sacrificed from 2-26 weeks after transfer. To separate the effects of testis feedback from a possible direct photoperiodic drive on the hypothalamus, males were bilaterally castrated, kept under LD or transferred to SD, and sacrificed from 2-14 weeks after transfer. Hypothalamic explants were incubated in a saline buffer for three periods of 15 min and exposed to KCl (60 mM) for 15 min. The return to basal values was followed for six periods of 15 min, then the explants were stimulated with copper complexed equimolarly with histidine (Cu/His, 200 microM) and prostaglandin E2 (PGE2, 10 microM). At the end of the incubation period, the concentration of GnRH remaining in the explants was measured. In intact males, GnRH release in vitro increased significantly between 2 and 4 weeks after transfer to short days; it returned to values similar to LD ones between 6 and 12 weeks, during the phase of testis involution. At the beginning of photorefractoriness (SD 14-18), it increased transiently and returned to values similar to LD ones from SD 20, during the testis spontaneous recrudescence. After castration, the in vitro GnRH release decreased significantly under LD and SD. The transfer of castrated hamsters to SD resulted in transient increases of GnRH release (SD 4, 8 and 14), and in a progressive loss of the explant's ability to release GnRH in vitro. These results showed a photoperiodic regulation of in vitro GnRH release and a testis feedback effect on this release. They demonstrated an inverse relationship between the readily releasable pool of GnRH and the circulating levels of gonadotrophins at the beginning of photosensitive and photorefractory phases and after castration.

Animals↗
PubMed2000

Genes upregulated during castration-induced rat prostatic apoptosis: cloning and characterization of new cDNAs.

OBJECTIVE: To isolate new cDNAs corresponding to genes whose expression is increased during castration-induced rat prostate apoptosis. MATERIALS AND METHODS: Differential display of mRNAs from 3-day castrated and normal rat ventral prostates was used to identify differentially expressed clones. Northern blots were hybridized to confirm the positive regulation of the candidates and to follow the change in their expression in the involuting rat prostate, and in thymocytes of dexamethazone-treated rats. RESULTS: Five cDNAs were cloned: one encoding ribosomal protein L7, one coding for the insulin-like growth factor binding protein-3 (IGFBP-3), and three whose products are unknown. After castration, all five genes had expression kinetics that closely paralleled the proportion of prostatic epithelial cells undergoing apoptosis. The gene encoding L7 and two of the unknown genes were also upregulated in glucocorticoid-induced programmed death in thymocytes. In addition to the IGFBP-3 gene, those coding for proteins IGFBP-4, -5 and -6 were also overexpressed in the involuting prostate of androgen-deprived rats. CONCLUSION: Five new genes were identified that are up-regulated during castration-induced rat prostate apoptosis, three of which are potentially involved in the common intracellular pathway leading to programmed cell death.

Animals↗
PubMed1993

Plasma levels of luteinizing hormone in intact and castrated photosensitive blackheaded buntings (Emberiza melanocephala) exposed to stimulatory and nonstimulatory photoperiods.

Experiments were performed to investigate the effects of castration and/or photostimulation on plasma luteinizing hormone (LH) in photosensitive blackhead buntings. Castration evoked a significant rise in plasma LH in birds held under 8 h light: 16 h darkness (8L:16D). On exposure to 18L:6D for 24 d, both the intact birds and the castrates exhibited a significant rise in plasma LH, although the change in LH levels in the castrates was approximately 8 times greater than in the intact birds. When control birds under 8L:16D which showed no change in plasma LH up to d 13 were transferred to a 36-h resonance cycle (8L:28D), plasma LH rose significantly within 4 cycles of the treatment. Furthermore, the intact buntings showed rapid increase and decrease in the plasma LH levels during a 16-wk exposure to long (16L:8D) but not to short (8L:16D) photoperiods. These results suggest that: i) the photoperiodic drive on LH secretion is inhibited by the testes; ii) the blackheaded bunting has a strong photoresponsive system; and iii) a circadian rhythm of photosensitivity is involved in the photoperiodic time measurement in this species.

Animals↗
PubMed1985

Estrogen uptake capacity of individual pituitary cell types from male and female rats one, fourteen and fifty days after castration.

A quantitative autoradiographic technique was combined with immunocytochemical staining to compare 3H-estrogen uptake in individual pituitary cell types 1, 14 or 50 days after castration in both male and female rats. Silver grains were counted over nuclei of immunocytochemically stained cells and means were computed for each cell type. The order of labelling intensity for all groups was gonadotropes greater than or equal to lactotropes = somatotropes greater than thyrotropes = corticotropes. In male rats 3H-estrogen uptake capacity in all of these cell types remained unchanged over the post-castration interval. Only gonadotropes from female rats demonstrated a significant change in estrogen uptake capacity over the intervals examined. Uptake in these cells increased by 137% between 1 and 50 days after ovariectomy. At both 14 and 50 days post-ovariectomy, gonadotropes concentrated significantly more radioactive label than either lactotropes or somatotropes. One day after castration, gonadotropes from females concentrated less 3H-estrogen than males while at 50 days after castration they concentrated significantly more than gonadotropes from male rats.

Animals↗
PubMed2000

Tamoxifen prevents bone loss in castrated male mice.

The selective estrogen receptor modulator tamoxifen was administered to intact and castrated male mice, and its effects on tibial bones and circulatory calcium, phosphate and testosterone were compared with controls and castrated animals. Tamoxifen in a dose used in humans for treatment of breast cancer decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone, but did not have any negative effect on bone density or mineral content in intact mice. When castrated mice with extraordinarily low concentrations of testosterone and weights of seminal vesicles were treated with tamoxifen, the changes in bone density and bone mineral resulting from castration were not only entirely prevented, but increased above the values of intact mice. At the same time, cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of femur was completely prevented by tamoxifen treatment. Pharmacological therapy with estrogen agonist on bone, tamoxifen in androgen deficient adult male mice prevents bone loss.

Animals↗
PubMed2002

Blood pressure, heart rate, hormonal and other acute responses to rubber-ring castration and tail docking of lambs.

AIM: To examine cardiovascular, hormonal and other physiological responses of 2-month-old lambs to rubber-ring castration and tail docking. METHODS: Twenty-two male lambs, well accustomed to handling and prepared with femoral artery and jugular vein cannulae, were studied during a 5 h control period and, at least 2 days later, for 1 h before and 4 h after castration and tail docking using rubber rings. Pressure recordings were made via femoral cannulae and blood samples for analysis of plasma constituents were taken from jugular cannulae. RESULTS: Mean systolic, diastolic and mean arterial blood pressure, heart rate and the plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol all increased markedly during the first 1 h after ring castration and tail docking. Although plasma ACTH and cortisol concentrations had returned to control levels by 2.5-3 h, blood pressures and heart rate were still elevated 4 h after ring application. In contrast, there were no significant changes in mean plasma concentrations of renin, electrolytes, minerals, glucose, lactate, urea, creatinine, total carbon dioxide and total proteins, plasma osmolality or the haematocrit after ring application. There were no significant changes in the mean values for any parameter during the 5 h control period or the 1 h period before ring application. CONCLUSION: Systolic, diastolic and mean arterial blood pressure and heart rate may be more sensitive than plasma ACTH or cortisol concentrations as indices of low-grade pain induced by ring castration and tail docking. Alternatively, it is possible that by 4 h after ring placement a small shift in sympathetic tone still persists in the absence of low-grade pain.

Journal Article↗
PubMed2005

Effects of age on the electroencephalographic response to castration in lambs anaesthetised using halothane in oxygen.

AIM: To use the electroencephalogram (EEG) to ascertain whether the response of the cerebral cortex to the noxious stimulus of castration varied with age in lambs. METHODS: Two groups of East Friesian lambs were selected according to age; the mean age of the younger group (n=21) was 12 (SD 2) days and the older group (n=20) was 29 (SD 1) days. Anaesthesia was induced via mask using 4% halothane in oxygen, and maintained using 1.5% halothane in oxygen at a flow rate of 4 L/min. Once a stable plane of anaesthesia had been achieved, data collection of EEG and electrocardiographic (ECG) readings commenced, and the lambs were castrated 15 min later, using rubber rings. Median and 95% spectral edge frequencies (F95) and total EEG power (ptot) were derived from data from the EEG. RESULTS: Following castration, there was an increase in the median frequency (F50) in the younger lambs (p=0.002), and an increase in ptot in both groups (p=0.05), which was of greater magnitude in the older lambs. There were no significant changes in the F95. Both younger and older lambs exhibited a transient bradycardia (p=0.001 and p=0.01, respectively). CONCLUSIONS: These differences in the cortical response between the two groups suggest that 2-week-old lambs undergo a qualitatively different perception of the noxious stimulus of castration compared to 4-week-old lambs.

Age Factors↗
PubMed1986

The effect of testosterone on the plasma disappearance rates of sulphadimidine and antipyrine in castrated dwarf goats.

Plasma disappearance of sulphadimidine and antipyrine was studied in adult castrated dwarf goats before and following pretreatment with testosterone. Comparison was made with entire males before and after castration. Testosterone pretreatment caused a significant increase in the apparent elimination half-life in castrates, whilst in entire males castration caused a significant decrease.

Animals↗
PubMed1989

[The energy preservation requirements of growing pigs of different sexes fed normal and high protein diets. 5. Comparison with the results obtained from castrated pigs, sows and boars].

In one experiment each with castrated pigs, sows and boars (hybrid pigs of line 150), two groups of six animals received rations containing 17 and 45% crude protein resp. over the complete test period from 35 to 130 kg (castrated pigs), 150 kg (sows), 170 kg live weight (boars) and passed alternatively through a total of 60 metabolism periods on growth and 48 on maintenance level. There were significant differences between the 3 categories of animals with regard to energy maintenance requirement in the relation of 100:105:110 for castrated pigs less than sows less than boars. In contrast to the estimated values derived from previous studies for energetic maintenance requirement of 650 kJ/kg LW0.62.d the measured values for all 3 animal categories are by approximately 50% higher. The protein content did not have an influence on the maintenance requirement of metabolizable energy of the animals. The utilization of metabolizable energy of the two rations for body energy retention corresponds to the expectations with regard to its dependence on nutrients. The requirement of metabolizable energy for protein and fat retention is 1.7:1.0. The energy content of the weight gain of boars was, on average, 85% of that of castrated pigs and sows. The studies of blood parameters did not show any deviations in the parameters tested.

Animal Feed↗
PubMed2004

The evolution of virulence when parasites cause host castration and gigantism.

It has been suggested that the harm parasites cause to their hosts is an unavoidable consequence of parasite reproduction with costs not only for the host but also for the parasite. Castrating parasites are thought to minimize their costs by reducing host fecundity, which may minimize the chances of killing both host and parasite prematurely. We conducted a series of experiments to understand the evolution of virulence of a castrating bacterium in the planktonic crustacean Daphnia magna. By manipulating food levels during the infection of D. magna with the bacterium Pasteuria ramosa, we showed that both antagonists are resource-limited and that a negative correlation between host and parasite reproduction exists, indicating resource competition among the antagonists. Pasteuria ramosa also induces enhanced growth of its hosts (gigantism), which we found to be negatively correlated with host fecundity but positively correlated with parasite reproduction. Because infected hosts never recovered from infections, we concluded that gigantism is beneficial only for the parasite. Hosts, however, have evolved counteradaptations. We showed that infected hosts have enhanced reproduction before castration. This shift to earlier reproduction increases overall host fecundity and compromises parasite reproduction. Finally, we showed that this resource conflict is subject to genetic variation among host and parasite genotypes within a population and is therefore likely to be an important force in the coevolution of virulence in this system. A verbal model is presented and suggests that the adaptive value of gigantism is to store host resources, which are liberated after parasitic castration for later use by the growing parasite. This hypothesis assumes that infections are long lasting, that is, that they have a high life expectancy.

Adaptation, Physiological↗
PubMed2002

The effect of melatonin administration on circulating plasma luteinizing hormone concentration in castrated White Leghorn roosters.

Melatonin (MLT) has a significant role in mammalian reproduction, with little or no effect in birds. In the present study we studied the role of MLT in regulation of luteinizing hormone (LH) secretion in castrated White Leghorn (WL) roosters. In Experiment 1, castrated WL roosters (n = 30) were divided into three groups, and each group (n = 10) was subdivided into two subgroups (n = 5). Birds in one subgroup received an injection of MLT at 5 mg (MLT-5), 20 mg (MLT-20), or 80 mg (MLT-80)/kg BW. Birds in the second subgroup were vehicle-injected and served as controls. Each dose of MLT was administered on a separate day at 1100 h. Blood was sampled 30 min before and 10, 30, 60, and 120 min after MLT or vehicle administration. Ten minutes after MLT administration, a significant reduction in plasma LH was observed in the MLT-20 and -80 groups, i.e., 70.3 +/- 8.3% and 62.2 +/- 4.1% of control values, respectively. In the MLT-80 group, plasma LH further declined to 42.1 +/- 9.7% of control values 60 min after injection. In Experiment 2, 18 castrated WL roosters were divided into three groups of six birds each. Two groups were injected with 80 mg MLT/kg BW at the beginning of the experiment; the second group received an additional dose of 80 mg MLT/ kg BW 140 min after the first injection. The third group was injected twice (as in second group) with vehicle and served as control. Blood was sampled 30 min before and 30, 60, 120, 170, 200, and 240 min after injection. Repeated MLT injection maintained low levels of plasma LH level until the end of the experiment. In Experiment 3, 10 castrated WL roosters were divided into two groups (n = 5). The first group was injected daily, for 10 d, with 80 mg MLT/kg BW, the second group was vehicle-treated and served as a control. At Day 3, there was a significant reduction in plasma LH level in the MLT-treated group, which continued for 7 d. This study demonstrates that, in birds, MLT suppresses LH secretion in a dose- and a time-related manner.

Animals↗
PubMed1986

Threshold for behavioral response to testosterone in old castrated male rhesus macaques.

The sexual behaviors of old, intact (N = 5) and old, castrated (N = 6) rhesus macaque males were compared in six series of pair tests with receptive females. The castrated monkeys were tested when untreated and when given five doses of testosterone propionate (TP; 0.004, 0.016, 0.064, 0.256, and 1.024 mg/kg of body weight) in consecutive months. The serum testosterone (T) level was determined for each male before and after each series of tests. When untreated, none of the castrated males ejaculated, and yawning was significantly less in these monkeys than in intact males-no other behavioral measures differed significantly. Within 2 weeks of daily injections of 0.004 mg of TP/kg, two males ejaculated, and all differences in measures of ejaculation were eliminated. A third male ejaculated after 1 week of treatment with 0.016 mg of TP/kg. Yawning values did not differ during and after treatment with 0.064 mg of TP/kg. Although final mean serum T levels were six times higher in castrated (24.3 ng/ml) than in intact males (4.2 ng/ml), sexual performance levels did not exceed those of intact males.

Aging↗
PubMed1989

Changes of norepinephrine levels, tyrosine hydroxylase and dopamine-beta-hydroxylase activities after castration and testosterone treatment in vas deferens of adult rats.

Norepinephrine levels and tyrosine hydroxylase and dopamine-beta-hydroxylase activities have been used to evaluate the effect of castration and testosterone treatment on the sympathetic innervation of the adult vas deferens. Castration was followed by a decrease in both norepinephrine content and tyrosine hydroxylase activity, even though the changes were not concomitant. Treatment of castrated animals with testosterone reversed the effect of castration on organ weight and norepinephrine content, but only a short-lasting increase in tyrosine hydroxylase activity occurred at the beginning of testosterone treatment. In contrast, the testosterone-induced recovery of norepinephrine content observed at this time was accompanied by a marked increase in dopamine-beta-hydroxylase activity. The results suggest that in rat vas deferens, norepinephrine levels are under androgenic control and that this regulation mainly involves changes in dopamine-beta-hydroxylase activity rather than a modulation of tyrosine hydroxylase.

Animals↗
PubMed1989

Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism.

Male rats were either unilaterally or bilaterally castrated, or were rendered cryptorchid when they were either 15 or 45 days old. Subsequently, blood was sampled over the next several weeks and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and immunoreactive inhibin-alpha (irI alpha) levels were measured by specific radioimmunoassays (RIAs). At the end of the experiment, gonadal expression of inhibin-alpha, inhibin-beta A, and inhibin-beta B subunits was measured by S1 nuclease analysis and in situ hybridization. In both age groups, bilateral castration (BC) produced the expected marked (p less than or equal to 0.01) increases in plasma LH and FSH levels, and concomitant decreases in T and irI alpha secretion within 1 - 2 days after surgery. In 15-day-old animals, unilateral castration (UC) significantly increased FSH and decreased circulating levels of irI alpha, but did not measurably alter LH or androgen production. At 7 days after surgery, the level of inhibin mRNA in the remaining testis was unchanged. In 45-day-old animals, UC caused a measurable increase in FSH, with little or no changes in the circulating levels of irI alpha. Plasma T levels were lowered (p less than or equal to 0.05) by UC; however, there were no statistical changes in LH levels in these UC rats. Finally, T administration markedly reversed UC-induced increase in FSH secretion in both age groups. Androgen therapy also interfered with inhibin release in 45-day-old, but not in 15-day-old rats. In rats 15 days old at the time of surgery, cryptorchidism produced a small but measurable increase (p less than or equal to 0.05) in LH release at Week 6 only, which was accompanied by a significant (p less than or equal to 0.01) decline in T secretion. Plasma FSH levels were elevated at all times in cryptorchid rats, and at 2, 4, and 6 wk, these levels were not statistically distinguishable (p greater than 0.05) from those of castrated animals. In this group of rats, cryptorchidism caused a transient increase (p less than or equal to 0.05) in irI alpha values 1 wk after surgery, but no changes at later times. Finally, measurement of testicular inhibin-alpha subunit messenger RNA (mRNA) levels showed an approximately 2-fold increase compared to total RNA levels in the testis. However, because of the significant decrease in total RNA levels per testis caused by cryptorchidism, the absolute change in inhibin-alpha subunit mRNA levels per testis corresponded to an approximately 3-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effects of gonadal steroids on follicle-stimulating hormone and luteinizing hormone secretion by pituitary cells from castrated and intact male rats.

The effectiveness of androgens in suppressing gonadotropin secretion declines with time following orchidectomy; however, the mechanism for this acquired resistance to androgen action is unknown. The role of the pituitary was studied by use of perifused rat pituitary cells and cells in monolayer culture. Pituitary cells from 7-wk-old intact male rats and rats that had been castrated 2 wk previously were treated with 10 nM testosterone (T) for 24 h; cells were then packed into perifusion chambers and stimulated with 2.5 nM GnRH for 2 min every hour for 8 h during which time T treatment was continued. T suppressed GnRH-stimulated LH secretion and LH pulse amplitude equally in both groups to approximately 60% of control values. Interpulse LH secretion was unchanged by T in either group. GnRH-stimulated FSH release was suppressed more (p less than 0.05) by T with cells from castrated rats than with cells from intact rats (76 +/- 4% vs. 90 +/- 2% of control; mean +/- SEM). By contrast, the action of T to increase interpulse basal FSH secretion was less (p less than 0.05) with cells from castrated rats (115 +/- 10% of control) than with cells from intact rats (146 +/- 6% of control). T treatment for 72 h also increased basal FSH secretion by pituitary cells in monolayer culture to a lesser extent with cells from castrated rats than with cells from intact rats (151 +/- 14% vs. 191 +/- 16% of control, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Persistent sexual behavior in castrated, recombinant inbred mice.

In contrast to other male mice, many hybrid B6D2F1 males continue to mate after being castrated in adulthood. This persistent sexual behavior in the castrated hybrids presumably is based upon heterozygosity that might occur within individual loci or between different loci. Those possibilities were discriminated by studying BXD recombinant inbred mice. In BXD strains, individual loci are homozygous, but heterozygosity has arisen between separate loci. Males in two of six BXD strains persisted in copulating for 5 mo after being castrated. Thus, it is concluded that retention of masculine sexual behavior in castrated mice is a function of heterozygosity between loci.

Animals↗