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Regional differences in testosterone effects on vasopressin receptors and on vasopressin immunoreactivity in intact and castrated Siberian hamsters.

Vasopressin binding sites were detected in the brain of the Siberian hamster, using [3H]vasopressin and a 125I-labelled linear vasopressin antagonist specific for V1 vasopressin receptors. In the ventromedial and premammillary nuclei, the density of the binding was lower in the females than in the males. The effect of castration and of testosterone replacement was assessed in males. Two distinct effects were observed. Orchidectomy diminished significantly the vasopressin binding in the ventromedial nucleus, an effect which was prevented by implantation of a mini-pump releasing testosterone. On the contrary, in the premammillary nucleus no significant differences were noticed following castration and testosterone treatment. In addition, vasopressin immunoreactivity was examined in males, in females and in castrated males. No sex differences were evident. However, in the bed nucleus of the stria terminalis and the lateral septal nucleus, castration decreased vasopressin immunoreactivity in either sex. This effect of castration was prevented by testosterone. Vasopressin immunoreactivity was detected neither in the ventromedial nor in the premammillary hypothalamic nuclei. Our observations suggest that, in adult Siberian hamster premammillary nucleus, the expression of vasopressin receptors is not controlled by gonadal steroids but is sex related and could be induced during fetal or early postnatal life.

Animals↗

Castration, sex steroids, and heterosexual behavior in adult male laboratory-housed stumptailed macaques (Macaca arctoides).

The sociosexual behaviors of six stable male-female pairs of stumptailed monkeys were studied in half-hour pair tests. Their performance before and after castration of the males was compared. The effects of replacement therapy with sex steroids on male-female interaction were studied. Also the effects of new females as sexual partners were investigated. Castration caused a significant decrease in sexual behavior. Individual males could display ejaculatory behavior up to about 1 year postcastration. Dihydrotestosterone propionate (75 mg/week/male) alone or in combination with estradiol benzoate (0.9 or 3 mg/week/male) was not effective in restoring sexual behavior to precastration levels in the three castrated males tested. Replacement therapy with testosterone propionate (75 or 10 mg/week/male) was effective in restoring copulatory behavior in half of the castrated males. In some males the introduction of a new female caused an increase in sexual activity, usually when sexual activity with their familiar partner was low. This occurred both in the castration condition and in the steroid treatment period, suggesting, that low activity was caused by low "motivation" and not by the inability to perform.

Androgens↗

The Ca2+-dependent protease inhibitor of rat ventral prostate: properties of the inhibitor and effects of castration on Ca2+-dependent protease and inhibitor activities.

1. The rat ventral prostate contains a heat stable inhibitor of Ca2+-dependent protease. This inhibitor was found to exist in a wide range of molecular weights (approx. 40-270 kDa) in adult rats. 2. However, in rats immediately post puberty (45 days of age) the inhibitor was predominantly of the higher molecular weight forms. 3. The inhibitor was also found in the dorsolateral and anterior (coagulating gland) prostate lobes but was of lower specific activity than in the ventral lobe. 4. Although the activities of the Ca2+-dependent protease and inhibitor decreased per ventral prostate gland after castration, these activities were not different during the first 10 days postcastration when expressed per g wet wt or per unit cytosol protein. 5. With a longer duration of castration, there was a decline in the specific activity (per unit protein) of the protease and an increase in that of the inhibitor. 6. Thus, the activities of the protease and inhibitor change in concert with the amount of cellular cytosol protein during the active period of castration-induced atrophy. 7. However, in long term castrated rats, functions carried out by the Ca2+-dependent protease may be effectively suppressed. 8. These data suggest that the Ca2+-activated protease probably is involved in the regulation of some metabolic processes in the active gland and is not prominent in the castration induced atrophy of the ventral prostate unless it functions through the proteolysis of some select protein(s).

Animals↗

Influence of estrogen on cholesterol esterification and fatty acid composition in serum lipoproteins of castrated rats.

Total, free and esterified cholesterol and its fatty acid composition were measured in the serum lipoproteins of castrated rats after estradiol administration. In general, castration and treatment with estradiol led to a decrease in total esterified cholesterol content. However, estradiol induced an effect opposite to that of castration on the fatty acid composition in VLDL. The effects were variable in HDL and insignificant in LDL. Similarly, the ratios of essential fatty acid to non-essential fatty acid (EFA/NEFA) and that to monoenoic acid (EFA/ME) were affected differently in castration and estradiol treatment in VLDL, but not in HDL or LDL. The pattern of lipid metabolism in castrated and estradiol-treated rats thus appears opposite to that described in human pathology.

Animals↗

Prepuberal social rearing conditions and sexual behavior in control and neonatally castrated male rats.

Male and female sexual behaviors were assessed in control and neonatally castrated male rats that had been housed with a female, a control male, or a neonatally castrated male from day 16 until adulthood. Prepuberal housing conditions had no differential effect on lordosis or ejaculatory potentials of neonatally castrated males tested as adults. A smaller percentage of control males raised with a neonatal castrate ejaculated than did animals housed with a female or a control male. However, a greater proportion of control males caged with a female showed lordosis than did those living with another control male or with a neonatal castrate. The data demonstrate the modulating effects which specific types of social stimulation experienced during early life have on sexual behaviors displayed in adulthood.

Androgens↗

Intermale aggression in mice: does hour of castration after birth influence adult behavior?

In the mouse, perinatally present testicular androgens promote the development of the propensity for adult intermale aggression. In the newborn male mouse plasma testosterone more than doubles during the first 2 h after birth and then falls rapidly to remain relatively low for the remainder of the 24-h period after birth. To study whether this surge in plasma testosterone influences aggressiveness we castrated some male mice within 1 h after birth i.e., before the surge. We castrated other males between 1.5-6 h after birth, or 1, 6, or 12 days after birth. Males were given testosterone as adults and tested for aggression for 5 weeks. Males castrated within 1 h after birth were not clearly different from males castrated 1.5-6 h after birth with respect to aggressive behavior, although males in both groups were substantially less aggressive than males castrated later in life. Thus, the perinatal surge in plasma testosterone in the mouse does not appear to make a unique contribution to the organization of mechanisms for intermale aggression. Rather, this surge is probably the initial stimulus that begins the postnatal process by which testicular hormones promote the development of the potential for adult aggressive behavior. This process appears to be complete by 6 days after birth.

Aggression↗

Effects of castration on behaviour and plasma cortisol concentrations in young lambs, kids and calves.

Behavioural and cortisol responses to the husbandry practice of castration with tight rubber rings were investigated in lambs and kids one day after birth and in hand reared calves aged one to seven days. There were three treatments: control handling and blood sampling, castration and, in lambs and kids only, intravenous adrenocorticotrophin injection (ACTH). The integrated cortisol responses (area under the cortisol curve) in lambs and kids were least in control, intermediate in castrated and greatest in ACTH animals. No cortisol responses were detected in control or castrated calves. The incidences of behaviour used to assess the intensity of distress apparently experienced in the different species corresponded generally with the magnitudes of the cortisol responses. Behavioural and cortisol responses together suggested that the distress caused by castration was greatest in lambs, intermediate in kids and least but not necessarily absent in hand reared calves.

Adrenocorticotropic Hormone↗

Effect of different methods of castration on behaviour and plasma cortisol in calves of three ages.

Calves of six, 21 and 42 days were either handled (controls) or castrated by Burdizzo, by surgical or by rubber ring techniques and their behaviour and plasma cortisol monitored for three hours after treatment. The rubber ring caused significant increases in active behaviour and abnormal postures for two hours compared with handled or castrated by Burdizzo and surgical techniques, and surgical techniques resulted in a significant increase in abnormal standing, particularly in the first 30 minutes. Abnormal behaviour and posture were recorded less frequently in six-day-old calves. The mean cortisol peaks for six-, 21- and 42-day-old calves were, respectively, 36, 31 and 23 nmol litre-1 in the handled groups; 60, 43 and 48 nmol litre-1 in the rubber ring groups; 77, 50 and 62 nmol litre-1 in the Burdizzo groups; and 106, 63 and 107 nmol litre-1 in the surgical groups. The greatest cortisol response occurred in 42-day-old surgically treated calves and the shortest response after Burdizzo castration. These responses suggest that irrespective of age, all methods of castration studied caused acute pain. Burdizzo castration appeared to produce the least pain, particularly in younger calves.

Age Factors↗

Naloxone inhibits mating and conditioned place preference for an estrous female in male rats soon after castration.

Three experiments were conducted to assess the role of endogenous opioids in controlling mating behavior and sexual reward in the male rat. In Experiment 1 SC administration of naloxone (0.5, 1.0, 5.0, or 10.0 mg/kg) significantly reduced mounting and ejaculation in male rats tested 14, but not 7 days, after castration. In Experiment 2 naloxone (5.0 mg/kg) administered SC to gonadally intact males, which had ejaculated repeatedly with one female until they were sexually sated, significantly inhibited the resumption of mating after the reintroduction of a female partner. One interpretation of these results is that naloxone attenuated the reward experienced by castrated and sexually sated males in the presence of an estrous female, thereby disrupting males' coital performance. This hypothesis was tested in Experiment 3 using a conditioned place preference paradigm in which males copulated with an estrous female in an initially "non-preferred" (white) compartment, whereas on alternate days they remained alone in an initially "preferred" (black) compartment. After 10 such conditioning sessions, males were either castrated or sham-operated. They later were given free access to both compartments in the absence of an estrous female. Seven days after conditioning and surgery, sham-operated, naloxone-injected males and both groups of castrates spent significantly less time than sham-operated, saline-injected controls in the initially "non-preferred" compartment. Fourteen days after conditioning and surgery castrated, naloxone-treated males spent significantly less time in the "non-preferred" compartment than males in the other three groups. Endogenous opioids may play an important role in the interpretation by males of the incentive motivational stimuli which emanate from an estrous female.

Animals↗

Distribution of androgen receptor-like immunoreactivity in the brains of intact and castrated male hamsters.

The distribution of androgen receptor-like (AR) immunoreactivity was mapped in brains of (a) intact, sham-castrated and (b) castrated male hamsters. The pattern of AR-immunoreactive (AR-ir) staining was, in general, similar to that reported for gonadal steroid autoradiography of the male hamster brain. Moreover, with one exception, AR-like staining was similar in intact and castrated males, and occurred in the medial preoptic area, bed nucleus of stria terminalis, amygdala, hippocampus, thalamus, and several hypothalamic nuclei including the periventricular, supraoptic, and ventromedial nuclei, and median eminence. However, while AR-ir labeling was virtually absent in the lateral septum of intact males, it was clearly present in the lateral septum of castrated males. The view that androgen receptors in brain generally decline after castration received no support from this study.

Animals↗

Effects of estradiol and estradiol-progesterone treatment on gonadotropin secretion in castrate aging female rats.

Estradiol-17 beta and estradiol-17 beta-progesterone were administered to aging female rats immediately after castration. Estradiol (1.6 micrograms) alone suppressed the castration hypersecretion of FSH in mature animals to 70% of the castration controls, but in 360-day-old and older animals, the inhibition was less than 10%. There was a decrease in the castration hypersecretion of LH by exogenous estradiol-17 beta with increasing age, but the pattern of suppression was similar in all animals, regardless of age. When a constant dose of estradiol-17 beta of 0.4 micrograms/kg body wt. was administered to castrate rats with varying doses of progesterone, it was shown that after 270 days of age the negative feedback effect of these steroids on FSH secretion was not found. Whereas, when progesterone of varying doses was administered with a constant dose of 0.8 micrograms/kg BW of estradiol-17 beta, it was shown that after 180 days of age the positive feedback effect of these steroids on FSH was absent. After 270 days of age the augmentation of LH secretion by estradiol-17 beta and a middle dose of progesterone was not apparent even though the negative feedback on LH was effective. A defect in positive and negative feedback effects of gonadal steroids on gonadotropin secretion may be causative to age-related changes in the estrous cycle of rats.

Aging↗

The effect of ventral nerve cord severance and male castration on female mating behavior, clutch size, and maternal care in the ring-legged earwig.

Mating is critical for the expression of oviposition and maternal care in the earwig, Euborellia annulipes; additionally, mating diminishes receptivity to additional mating and promotes a decline in juvenile hormone synthesis at the end of the gonadotrophic cycle (in contrast to most insect species wherein mating stimulates juvenile hormone production). We report here that severance of the ventral nerve cord of virgin females similarly promoted egg deposition and maternal care of eggs, diminished mating receptivity, and elicited a timely decline in juvenile hormone biosynthesis. Mating of intact females to adult males that were castrated as larvae did not abolish oviposition; however, clutch size was reduced, and no eggs developed. Such castrated males had smaller seminal vesicles than did intact males, presumably attributable to lack of sperm in castrated males. In contrast, mating of intact females to males castrated on day 1 of adult life did not reduce clutch size compared with those of sham-operated animals and did not abolish fertilization; in fact, these castrated males produced viable offspring after six matings. These results are consistent with the notion that ventral nerve cord severance mimicked mating in intact animals. Following mating, the ventral nerve cord likely is a conduit to release the brain from inhibiting oviposition and maternal care. The presence of sperm in the spermatheca is not necessary for release of this inhibition but may modulate clutch size.

Animals↗

Cholinergic regulation of Na+-K+-ATPase activity in rat parotid gland: changes after castration.

In this study, we investigated the different signalling pathways involved in muscarinic acetylcholine M(3) receptor-dependent modulation of Na(+)-K(+)-ATPase in parotid glands from normal and castrated rats. Carbachol inhibited the enzyme activity in parotid glands from control rats while it stimulated the enzyme activity in castrated rats. The inhibition of Ca(2+) calmodulin by trifluoperazine abolished the inhibitory effect of carbachol in control rats, while the inhibition of protein kinase C by staurosporine stimulated Na(+)-K(+)-ATPase. In castrated rats, trifluoperazine inhibited the carbachol-stimulant effect while staurosporine had no effect. Results indicate that in control glands the activation of a phospholipid-Ca(2+) calmodulin-dependent protein kinase C is responsible for the inhibitory effect of carbachol on Na(+)-K(+)-ATPase activity. In castrated rats, the activation of the enzyme by carbachol is regulated by its Ca(2+) calmodulin-stimulating action, and not by activation of protein kinase C. The activation of the Na(+)-K(+)-ATPase observed in castrated rats resulted in a decrease in carbachol-induced net K(+) efflux and thereby could decrease salivary fluid production.

Animals↗

Testosterone and zinc supplementation in castrated rats: Effects on plasma leptin levels and relation with LH, FSH and testosterone.

The present study aims to examine how zinc and testosterone supplementation, in combination and separately, affect plasma LH, FSH and leptin levels in castrated rats. Eighty experimental animals used in the study were allocated to 8 groups, each containing an equal number of rats. Group 1, control group; Group 2, castration group; Group 3, testosterone group (5 mg/kg/day); Group 4, zinc-supplemented group (3 mg/kg/day); Group 5, testosterone and zinc-supplemented group; Group 6, zinc-supplemented castration group; Group 7, testosterone and castration group; and Group 8, zinc-supplemented, testosterone and castration group. Plasma zinc, leptin, LH, FSH and free and total testosterone levels were determined in the blood samples collected from the animals by decapitation. Group 2 had the highest leptin levels and together with group 6, it also showed the highest LH and FSH levels (p<0.01). The lowest leptin levels were observed in groups 3 and 7 (p<0.01). Leptin levels in groups 4 and 6 were higher than those in groups 1, 5 and 8 (p<0.01). LH levels in group 4 were lower than those in groups 2 and 6 and higher than those in all other groups (p<0.01). Free and total testosterone levels in groups 7 and 8 were lower than those in groups 3 and 5, but higher than those in all other groups (p<0.01). Plasma LH levels may be more effective than testosterone on plasma leptin and zinc may be an important mediator of the effect LH has on leptin.

Animals↗

Surgical and chemical castration induce differential histological response in prostate lobes of Mongolian gerbil.

The present study describes the short-term alterations in the prostate ventral and dorsal lobe of the adult Mongolian gerbil, in response to two different androgen suppression approaches. Groups (n=6) of 16-week-old gerbils were maintained intact or subjected, either to the bilateral surgical castration 1 week previously or to daily subcutaneous injections of Flutamide (10mg/kg body weight) for 7 days. The main microscopic features of both prostate lobes in these groups were compared using conventional paraffin tissue sections, measurements of acinar epithelial height and stereological data of main gland components (acini, collagen fibers and fibromuscular stroma). Marked alterations were observed in the basement membrane of the ventral lobe after both surgical and chemical castration, such as an increase in thickness and collagen staining. A low degree of epithelial atrophy was detected in the dorsal lobe following both androgen suppression approaches in comparison with that found in the ventral lobe, indicating that this lobe is not so responsive to testosterone ablation induced by castration or Flutamide treatment, at least insofar as secretory activity is concerned. However, the dorsal lobe exhibited marked stromal modification, such as an increase in collagen fibers following castration and an increase in fibromuscular stroma following Flutamide-treatment. Thus, the histological and quantitative data indicates a differential short-term response of the prostate dorsal lobe to surgical castration and Flutamide therapy, suggesting the existence of lobe-specific mechanisms for stromal remodeling.

Androgen Antagonists↗

Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft.

Androgen receptor expression was analyzed in the CWR22 human prostate cancer xenograft model to better understand its role in prostate cancer recurrence after castration. In androgen-dependent tumors, 98.5% of tumor cell nuclei expressed androgen receptor with a mean optical density of 0.26 +/- 0.01. On day 2 after castration androgen deprivation decreased immunostained cells to 2% that stained weakly (mean optical density, 0.16 +/- 0.08). Cellular proliferation measured using Ki-67 revealed <1% immunostained cells on day 6. Androgen receptor immunostained cells increased to 63% on day 6 and 84% on day 32 although immunostaining remained weak. Cellular proliferation was undetectable beyond day 6 after castration until multiple foci of 5 to 20 proliferating cells became apparent on day 120. These foci expressed increased levels of prostate-specific antigen, an androgen receptor-regulated gene product. In tumors recurrent 150 days after castration androgen receptor-immunostaining intensity was similar to CWR22 tumors from intact mice although the percentage of cells immunostained was more variable. The appearance of proliferating tumor cells that expressed androgen receptor and prostate-specific antigen 120 days after castration suggests that these cells represent the origin of recurrent tumors.

Androgens↗

Effects of testosterone on pedicle formation and its transformation to antler in castrated male, freemartin and normal female red deer (Cervus elaphus).

Pedicles and antlers are male deer secondary sexual characters. As such, development of these structures is under the control of androgen hormones. Pedicle growth is caused by increasing and elevated plasma testosterone (T) levels, whereas first antler transformation from a fully formed pedicle occurs when the T levels are decreasing. Castration prior to pedicle initiation abrogates future pedicle and antler formation. Female deer also have the potential to develop pedicles and antlers, but they do not normally express this phenotype due to lack of sufficient androgen stimulation. Previous studies have shown that female white-tailed deer could be readily induced to grow pedicles as well as antlers by singular administration of exogenous androgens (EA), but in red deer (Cervus elaphus) singular or irregular EA treatment could only stimulate castrated male, normal or ovariectomised females to grow pedicles, but not antlers. The present study was set out to test whether these EA-induced pedicles in red deer failed to give rise to antlers was because they were constitutively incapable of doing so, or because the plasma T profile naturally exhibited in intact stags was not achieved by the androgen treatment used in these previous studies. Eight castrated red deer stag calves, 3 freemartins (females which were born co-twin to males), and 3 normal female red deer were used in the present study and treated with EA, either as biweekly injections for the castrates or as implants for freemartin and females until the late stage of pedicle growth. Blood sampling was carried out biweekly for the analyses of plasma T and IGF1 concentration. The results showed that the natural plasma T profile in the experimental deer was successfully mimicked through regular EA treatment and subsequent withdrawal at late pedicle growth stage. All castrated males, 2 out of 3 freemartin, and 1 out of 3 normal female red deer formed not only pedicles, but also antlers. Based on these results, we conclude that EA-induced pedicles at least in red deer of the genus Cervus, like those in the genus Odocoileus, are constitutively capable of giving rise to antlers, if they are of sufficient height.

Animals↗

Effects of castration and diabetes mellitus on cholinergic responsiveness and muscarinic receptors in the rat vas deferens.

Studies were carried out to compare the effects of diabetes mellitus and castration on the muscarinic responsiveness of rat vasa deferentia. One and two months after castration or after streptozotocin-induced diabetes, there were significant decreases in serum testosterone levels, accompanied by significant decreases in vas deferens weights, protein contents, and protein concentrations. However, contractile responses of vasa deferentia from streptozotocin-diabetic or castrated rats to carbachol were significantly increased compared to controls. These changes were accompanied by increases in Kd and decreases in Bmax (pm/tissue) for 3H-quinuclidinyl benzilate (QNB) binding. Contractile responses and QNB binding were also studied in the spontaneously diabetic BB/W or rat, a less severely diabetic model than the streptozotocin-diabetic rat. Ninety days after the onset of diabetes in the BB rat, there was an increase in the contractile response to carbachol. There were qualitatively similar but smaller changes in vas deferens weights, protein contents, protein concentrations, and QNB binding than in the streptozotocin-diabetic rats. The data show that diabetes and castration increased the contractile responses of vasa deferentia despite decreases in protein content and in the number of muscarinic receptors. The results suggest that muscarinic receptor-effector coupling is more efficient in vasa deferentia from castrated or diabetic rats, resulting in a greater contractile response to cholinergic agonists.

Animals↗