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Differential effects of estrogen and androgen on locomotor activity induced in castrated male rats by amphetamine, a novel environment, or apomorphine.

Four experiments were conducted using male rats to determine whether testosterone (T), or its neural metabolites estradiol (E2) and 5 alpha-dihydrotestosterone (DHT), influence the expression of locomotor activity, which is thought to depend in part on the activation of mesolimbic dopaminergic neurons. Subcutaneous implantation of silastic capsules containing E2, but not T or DHT, caused a significant increase in the amount of activity displayed by castrated rats which had been habituated to infrared photobeam activity cages prior to receiving an i.p. injection of D-amphetamine sulfate (1.5 mg/kg). Administration of E2, but not T or DHT, also significantly increased the amount of activity which other groups of castrated rats displayed when they were first placed in the photobeam cages. Likewise, administration of E2 but not T or DHT, to castrated rats which had previously received bilateral injections of 6-hydroxydopamine into the nucleus accumbens septi, caused a significant increase in the activity displayed in response to an i.p. injection of apomorphine HCl (1.0 mg/kg). However, administration of estrogen or androgen to castrated rats which were neurologically intact had no effect on the amount of stereotyped behavior displayed in response to increasing doses (1.0, 2.0 and 4.0 mg/kg) of apomorphine. It is suggested that the selective, facilitatory effect of E2 on drug- and novelty-induced locomotor activity resulted from increased postsynaptic receptor activation at dopaminergic synapses in the nucleus accumbens septi.

Animals↗

The effect of testosterone and of castration on anococcygeus muscle contractility and on plasma corticosterone levels in the rat.

The effect of testosterone and of castration on the contractility of the rat anococcygeus muscle, on plasma corticosterone concentrations, and on adrenal gland weights, was investigated. Castration was without effect on smooth muscle reactivity. However, testosterone increased muscle contractility to both NA and ACh, when given to control or castrated rats. Castration reduced both plasma corticosterone and adrenal gland weight, and this effect could be reversed by testosterone. It is concluded that changes in circulating testosterone levels cannot explain the lack of effect of adrenalectomy on muscle contractility. The possible mechanism of action of testosterone is discussed.

Acetylcholine↗

Influence of gonadotropin-releasing hormone on castration-induced 'depression' in mice: a behavioral and binding study.

Long-term (33-35 days) castration caused a significant increase in the duration of immobility of male and female mice in the tail suspension test (an animal model of depression), and a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in the cerebral cortex of male mice. In the tail suspension test, gonadotropin-releasing hormone (GnRH), s.c. injected 3 times at 3-h intervals at doses of 0.2, 2 or 20 micrograms/kg, did not significantly modify the duration of immobility of castrated animals and did not reduce that of sham-operated ones, while desipramine (20 mg/kg s.c. 1 h before testing) restored immobility to normal in castrated animals and reduced it significantly in sham-operated ones. The same treatment schedule with GnRH produced an increase in the number of [3H]imipramine Bmax in cortical membranes that was statistically significant at the dose of 2 micrograms/kg. It is concluded that the castration-induced depression-like behavior in mice seems not to be due to the decreased levels and release of GnRH, and that GnRH has no antidepressant-like effect in mice, at least at our dose levels; however, GnRH seems to increase the number of cortical [3H]imipramine binding sites.

Animals↗

Prolactin is associated with the development of photorefractoriness in intact, castrated, and testosterone-implanted starlings.

Using radioimmunoassays, prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in the plasma of intact, castrated, and testosterone-implanted male starlings. Two groups of birds (intact and castrated males) were transferred when photosensitive from short (8-hr) to long (16-hr) day lengths; in both cases plasma prolactin levels increased steadily reaching a peak after 5 weeks of photostimulation, at the time of the onset of photorefractoriness . Three groups ( intacts , castrates, and castrates implanted with Silastic capsules containing testosterone) were exposed to day lengths increasing by 30 min per week from 8 to 16 hr. Again, prolactin levels increased in a similar fashion in all three groups at the time of refractoriness, which occurred when the day length reached 15-16 hr. Thus the timing of photorefractoriness and the associated rise in prolactin secretion which occur in response to photostimulation do not depend upon the presence of the gonads and are not affected when testosterone is maintained at a constant high level. Nor is the increase in prolactin altered when the cycle of gonadotrophin secretion which normally precedes it is completely suppressed by the implantation of a testosterone capsule. It would seem that prolactin secretion in the starling is stimulated by transfer from short to long day lengths, but not as a consequence of high gonadotrophin or androgen secretion rates.

Animals↗

The effects of castration and/or methimazole feeding on the pituitary response to temperature extremes by cockerels.

The pituitary of goitrogen-treated White Leghorn cockerels is smaller in size than control birds and the pituitaries of castrated cockerels is nearly twice the size of control birds. The pituitary cells generated by these treatments may not be functional thyrotrophs or gonadotrophs and may not be able to respond to their usual stimuli. Low ambient temperature is a well-known stimulus to the thyroid gland acting through pituitary TSH. Cyclic-AMP-dependent protein kinase activity levels are used here as an index of cellular activity in the pituitary and thyroid glands. Castrated cockerels with or without methimazole treatment do not have an increased pituitary cAMP-dependent protein kinase activity in cold. Methimazole-treated birds have an exaggerated pituitary protein kinase response to cold stress when compared with controls. Pituitary cAMP-dependent protein kinase activity is paralleled by a similar activity increase in the thyroid gland of methimazole-treated cockerels and no increase in the thyroid of castrated birds. Castrated birds at all temperatures have an elevated thyroid cAMP-dependent protein kinase activity ratio which is interpreted as the result of removal of testosterone inhibition.

Animals↗

Investigation of familiar and novel chemosensory stimuli by golden hamsters: effects of castration and testosterone replacement.

Estrous hamsters secrete an odorous vaginal discharge that intact male hamsters investigate vigorously during copulatory behavior. Castrated animals are not attracted to this vaginal discharge. In this study we observed that repeated exposure of intact and castrated hamsters to this vaginal discharge reliably produced habituation of investigatory behavior. Presentation of the odor from a novel female to a habituated male caused an increase in investigation (dishabituation). Castration produced a decrease in investigation within 1 week of surgery. However, the surgery did not produce a decrease in dishabituation until 3 months afterward. Testosterone treatment increased chemosensory investigation in castrated animals. It seems likely that the dishabituation observed in this study may represent a sensory component of the Coolidge Effect.

Animals↗

The release of pituitary gonadotrophins by luteinizing hormone releasing hormone in the intact, castrated and aspermatogenic rat.

The change in serum gonadotrophin concentration in response to synthetic Luteinizing Hormone Releasing Hormone (LHRH - 400 ng i.v.) was investigated under barbiturate anaesthesia in adult male rats either chronically castrated, rendered aspermatogenic by the administration of alpha-chlorohydrin 12-16 weeks previously (to remove inhibin), or treated with vehicle. A single injection of LHRH increased serum LH and FSH concentrations similarly in both intact and aspermatogenic rats. In castrated rats the amount of LH released was much greater and the FSH secretion sustained. A second injection produced a similar increase although a second peak of FSH could not be detected in castrated rats as the FSH level was still elevated. The increase in LH levels was two to three times larger in response to the second injection of LHRH than to the first in all groups. The results do not support the hypothesis that the enhanced gonadotropin response to castration in the aspermatogenic rat is due to increased pituitary sensitivity to LHRH.

Animals↗

Immunoreactive beta-endorphin in the plasma, pituitary and hypothalamus of young female rats on the day of estrus and intact and chronically castrated old constant estrous female rats.

Immunoreactive beta-endorphin (IR-beta-ENDO) was compared in the plasma, pituitary and hypothalamus of young female rats on the day of estrus and old constant estrous (CE) female rats, and in intact and chronically castrated old CE female rats. The concentration of IR-beta-ENDO in the plasma and the content and concentration of IR-beta-ENDO in the neurointermediate lobe of the pituitary were significantly greater in the old CE female rats than in the young female rats on the day of estrus. The content and concentration of IR-beta-ENDO in the anterior pituitary and hypothalamus were similar in the two age groups. To determine if estrogen contributed to the increase in plasma and pituitary levels of IR-beta-ENDO observed in the old animals, a group of old CE female rats were castrated and compared to sham operated control CE rats. Thirty days after castration, levels of plasma, pituitary and hypothalamic IR-beta-ENDO were comparable in the intact and the chronically castrated old female rats. These data indicate that in old CE female rats, plasma and pituitary IR-beta-ENDO are significantly increased in comparison to young female rats on the day of estrus, and that these increased levels of IR-beta-ENDO observed in old female rats do not appear to be influenced by gonadal estrogen.

Aging↗

Temporal effects of castration on emotionality and shock-induced aggression in adult male rats.

Alterations in shock-induced aggressive behavior, general emotional reactivity and flinch thresholds in 61 and 82 day old male rats were analyzed at either 3 or 6 weeks following castration. Castrated animals were significantly less aggressive than sham-operated controls at the 6 week but not the 3 week interval. These findings could not be attributed to changes in flinch threshold as neither treatment nor time affected this measure. With regard to emotionality, castrated animals were significantly more reactive than the control animals at the 3 week but not 6 week interval. The data are interpreted as indicating that castration altered shock-induced aggression by preventing a maturational increase in such behavior. These behavioral alterations are compared to previously reported time-dependent changes in brain monoaminergic dynamics following gonadectomy. The conclusions support the concept of a necessary balance between catecholaminergic and serotonergic systems with regard to affective behavior.

Age Factors↗

Castration and reproductive behavior in the paradise fish, Macropodus opercularis (L.) (Osteichthyes: Belontiidae).

The effects of castration on male spawning behavior, nestbuilding and fertility were measured in a five day spawning trial with an intact female. Spawning and fertility decreased one week following castration while nestbuilding was unaffected. Sham operated males showed normal spawning and fertility. Two weeks postoperatively, fertility and spawning were increased paralleling partial regeneration of the testes. The antigonadotropin methallibure blocked testes regeneration and recovery of spawning in castrated males but it had no effect on reproductive functions of intact males. Spawning did not decrease in one-week castrated males which were administered testosterone enathanate. The results suggest that gonadal androgen facilitates sexual behavior in Macropodus.

Animals↗

Effect of castration and subsequent substitution with testosterone, dihydrotestosterone and oestradiol on sexual preference behaviour in the male rat.

In the present study effects of castration and subsequent hormonal substitution on the partner-preference behaviour of the male rat are investigated. For the determination of this behaviour a residential plus-maze is used. Castration of a male rat leads to the disappearance of preference behaviour after a few weeks. Subsequent administration of testosterone by means of a silastic implant restores this behaviour within a few weeks. Castrated male rats with a silastic implant containing dihydrotestosterone will not seek contact with the oestrous female rat. Oestradiol-implanted castrated male rats show the same behaviour in the residential plus-maze as do intact male rats. It is concluded that in the male rat gonadal hormones have an effect on the processing of the signals which an oestrous female rat emits to attract a male.

Animals↗

Characterization of separated prostatic and phosphatase forms in normal and castrated rats.

We have investigated the effects of castration and androgen replacement on the kinetic characteristics of rat prostatic acid phosphatases (AP). Chromatography on DEAE-cellulose DE-23 and on Sephacryl S-200 allowed the separation of lysosomal (S-1) and secretory (S-3) forms of AP. In addition, these techniques revealed a third enzymic form (S-2), which eluted in the void volume of the Sephacryl S-200 column and which occurred in significant amounts only 15 days after castration. The S-2 form was extremely resistant (Ki 1500 microM) to L-tartrate inhibition in the 15-day post-castration rat which is in contrast to the behaviour of S-2 (Ki 145 microM) in control animals. The appearance of this unidentified AP form can explain the dramatic drop in the per cent inhibition of total rat AP observed between 7 and 15 days post-castration.

Acid Phosphatase↗

Aminopeptidases of the rat prostatic complex and seminal vesicles: secretion and effect of castration.

Aminopeptidases hydrolysing L-leucine-beta-naphthylamine (LeuNA), L-alanine-beta-naphthylamide (AlaNA) and L-arginine-beta-naphthylamide (ArgNA) were studied in tissue homogenates of various parts of the rat prostatic complex and seminal vesicles after castration as well as in their 'cellular' and 'secretory' compartments. The 'secretory' fluids were also fractionated by chromatofocusing to reveal the enzymes possibly secreted by the glands. After castration the ventral prostate showed a temporary increase of LeuNA and a continuous rise of AlaNA hydrolysis, while ArgNA hydrolysis remained unaltered. Its 'secretory' fluid contained high hydrolysis rates of the substrates and chromatofocusing revealed two activity peaks with pI values of 6.2 and 5.4. In the lateral prostate no activity changes were recorded after castration. The 'secretory' fluid contained low enzyme activities and the fractionation showed one enzyme activity with pI 5.4. The posterior prostate, coagulating glands and seminal vesicles showed high hydrolysis rates of ArgNA with a rapid decline after castration. The 'secretory' fluid of posterior prostate contained rather low activity levels and in chromatofocusing two activity peaks with pI values of 6.2 and 5.4 were found. The 'secretory' fluid of coagulating gland contained a strong hydrolysis of ArgNA and chromatofocusing gave two activities with pI values of 5.4 and 5.1. The latter seemed to hydrolyse only ArgNA. The viscous secretion of the seminal vesicles contained very low aminopeptidase activities and chromatofocusing also showed a poor result. It is concluded that the various parts of the rat prostatic complex differ in their aminopeptidase composition. Only part of these enzymes appears to be secretory and controlled by testosterone. The major contribution to the seminal plasma aminopeptidase activity seems to derive from the ventral prostate and the coagulating gland.

Aminopeptidases↗

Different patterns of filipin-sterol labeling in prostate nuclear membranes from normal and castrated rats.

Filipin was used as cytochemical probe for sterol detection in freeze-fractured prostate nuclear membranes from rats under different hormonal conditions. Isolated prostate acini and nuclei were fixed in glutaraldehyde and post-treated with filipin, according to Robinson and Karnovsky (1980). In general, most plasma and intracellular cytoplasmic membranes displayed a marked response to filipin in either epithelial and stromal cells from normal and castrated animals. Nuclear membranes from epithelial secretory cells were systematically negative to filipin labeling in normal animals, although after castration a positive response was detected. Stromal nuclear membranes were labeled both in normal and castrated animals. Filipin-treated isolated nuclei displayed the same overall labeling pattern but there was a different distribution of induced deformations relative to intact cell nuclei. These observations indicate that: a) nuclear membranes from different cell types have different responses to filipin; b) a change in the molecular organization of nuclear membranes from prostate secretory cells follow castration; c) nuclei isolation affects the distribution of filipin induced deformations on the membranes.

Animals↗

The critical role of familiar urine odor in diminishing territorial aggression toward a castrated intruder in mice.

Sensory chemo-signals conveying information on sex and familiarity are important to the manifestation of aggressive behaviors in male mice. In this study, we examined the role of familiarity conveyed by urine odor in the induction of aggressive behavior using a resident-intruder paradigm. First, an intact ICR male mouse (resident) was grouped with a castrated DBA mouse (cage-mate) and a female ICR mouse to allow the resident mouse to establish its territory. The resident male showed vigorous aggression, not only toward intact male DBA intruders, but also toward unfamiliar castrated DBA mice (UFC). In contrast, the aggression was markedly reduced toward its castrated DBA cage-mate. Next, to reveal how residents discriminate their cage-mates from unfamiliar intruders, we examined whether urine odor affected this familiarity-related aggression. When part of the body surface of a UFC was swabbed with the urine of a resident's cage-mate, the resident attacked the UFC much less often. These results suggest that the information about familiarity conveyed by urine odor plays an important role in controlling the territorial aggression of a resident male mouse toward castrated intruders.

Aggression↗

Influence of neonatal castration or neonatal anti-gonadotropin treatment on fertility, phallus development, and male sexual behavior in the mouse.

Male mice were castrated on the day of birth or were treated with anti-gonadotropin serum (AGS) successively on days 1, 3, and 5 of age. When the adult AGS-treated males were compared with normal rabbit serum (NRS)-treated males with respect to fertility, male sexual behavior, gonadotropin release, body size, and penis size it was found that: (1) fertility of AGS-treated males did not differ from that of NRS-treated males; (2) AGS-treated males showed a significant reduction in penis size, compared with NRS-treated males; (3) both groups showed high levels of male sexual behavior; (4) neither group showed the capacity to support ovulation in ovarian grafts from immature mice. It was also observed that the fertility of female mice treated with AGS on days 1, 3, and 5 of age did not differ from that of control females treated with comparable doses of NRS. Male mice castrated at birth showed a significant reduction in male sexual behavior and penis size compared with males first sham-operated at birth then castrated at 25 days of age. Thus, males castrated at birth were similar to males receiving AGS in infancy, except for sex behavior. The results suggest that the neonatal pituitary in the mouse may not have an important role in the process of sexual differentiation. Previous data for the male rat were compared with those for the mouse.

Animals↗

Effects of castration and exogenous testosterone supplementation in an animal model of penile erection.

The dependence of erectile behavior on androgen functioning is well established. Castration produces loss of both libido and potency in man and animals. The present study, using an animal model for potency, demonstrates the dependence of centrally induced erectile behavior on an intact androgen milieu. Castrated rats failed to produce an erection in response to apomorphine, an agent shown to produce erection in nearly all normal rats. Administration of exogenous testosterone propionate in dosages exceeding 60 micrograms./kg. produced a significant increase in erectile behavior. Yawning, an essentially parallel phenomenon to the stimulation of the erectile response, was also decreased following castration and responded similarly to increasing amounts of exogenous testosterone, demonstrating the influence of androgen functioning on the central nervous system. It was concluded that testosterone is a necessary prerequisite for the maintenance of a centrally induced erectile and yawning response. In an animal model of penile erection, testosterone increases the number of erections in a dose-dependent manner in castrated rats. The dependence of the erectile response on testosterone is, at least in part, centrally mediated.

Animals↗

Proliferative response of rat accessory sex organs to dietary sex hormones after castration or initial dietary administration of estrogen.

The hormone dependent proliferative response of five accessory sex organs was examined subsequent to castration-induced or estrogen-induced atrophy using male six-week-old F344 rats. Three weeks after castration, rats were treated with dietary methyltestosterone (300 ppm), ethinyl estradiol (0.75 ppm) or methyltestosterone plus ethinyl estradiol for up to 17 days. Cell proliferation was assessed by 3H-thymidine incorporation as determined from labelling indices using autoradiography. The maximum labelling indices which appeared on days 2 or 3 of administration of methyltestosterone were 24.3, 8.4, 9.6, 21.6 and 13.7% for the ventral, lateral and dorsal prostate, seminal vesicle and coagulating glands, respectively. Combined methyltestosterone and ethinyl estradiol induced mild proliferative responses whereas ethinyl estradiol did not. In a further group of non-castrated rats which were pretreated with dietary ethinyl estradiol for three weeks and then given methyltestosterone, the maximum labelling indices were about 70 to 80% of that in castrated rats.

Animals↗