Effects of intracranial implants of testosterone propionate on intermale aggression in the castrated male mouse

Three experiments were conducted in order to assess the effects of intracranial implants of testosterone propionate (TP) on intermale aggression in the castrate male CF-1 mouse. In Experiment 1, seven groups received bilateral implants containing a total of 27 μg crystalline TP into the septum, neocortex, lateral ventricles, preoptic-anterior hypothalamus, hippocampus, medial reticular formation, and subcutaneously, and were tested 2 and 4 days after treatment. An eighth group received blank pellets in the brain. Animals receiving septal or lateral ventricle implants fought significantly more than other groups on trial 1. This difference had disappeared by trial 2, indicating diffusion of the hormone. The diffusion was corroborated by significant seminal vesicle growth. In Experiment 2 animals received bilateral implants of a total of 4.5 μg TP in paraffin or a blank pellet into the septum, preoptic-anterior hypothalamus, cortex, amygdala, olfactory bulbs, medial reticular formation, or subcutaneously. None of these treatments proved effective for activating aggression. Experiment 3 explored the activational effects of 10 μg of TP implanted bilaterally into the same areas as in Experiment 2, excluding the olfactory bulbs and cortex. Implants into the septum were followed by significantly increased fighting. Implants into the preoptic area were only marginally effective whereas the remaining two areas were not responsive to hormone treatment and did not differ from control animals. No seminal vesicle growth was detected as a result of the hormone treatments. These results would indicate that the septum is important in the control of androgen-dependent, intermale aggression in the male CF-1 mouse.     

Correlated effects of the Y-chromosome of mice on developmental changes in testosterone levels and intermale aggression.

Serum testosterone (T) was studied developmentally in DBA/1/Bg and C57BL/10/Bg inbred mice, as well as in their reciprocal F1 hybrids. Testosterone determinations were made using a radioimmunoassay. At 35 and 40 days $\text{post partum}$, DBA/1/Bg mice had higher levels of T than C57BL/10/Bg males. Comparison of the regression coefficients for the serum T values over days 30, 35, 40, and 50 also indicated statistical differences in the two curves of developmental changes in T. The pubertal rise in B10D1F1 but not D1B10F1 males was found to be steeper in slope over days 30, 35, 40, and 50 than that of C57BL/10/Bg males. These data suggest that during the pubertal period there may be a more rapid increase in serum T titer associated with the DBA/1 Y-chromosome. However, the developmental curves of T for the two reciprocal hybrids were not statistically different from each other or from that of the DBA/1/Bg males. These findings are suggestive of a Y-chromosome effect on developmental changes in T and of a genetic correlation with intermale aggression.     

A quantitative study of serum testosterone,sex accessory organ growth,and the development of intermale aggression in the mouse

Radioimmunoassay of serum testosterone (T) was used to characterize circulating T levels in mice from birth to sexual maturity. Until 25 days of age, serum T levels ranged from 1 to 4 ng/ml. A significant increase in T concentrations was observed in 30-day-old males, followed by a secondary rise in serum T between Days 45 and 50 of life. The latter increment was associated with the appearance of extreme individual variation in circulating T levels which was also observed in adult (120 days) males. The most rapid growth of accessory sex organs occurred between 30 and 50 days of age, the period preceding attainment of peak serum-T levels. The first incidence of intermale aggression coincided with a prepubertal rise in circulating T, but adult levels of fighting were present prior to the secondary increase in T observed between 45 and 50 days of age. Although animals involved in a fight did not differ with respect to weight of the accessory sex organs or serum T concentrations, the male that weighed more than his opponent usually won an encounter. Compared to males in encounters in which no fighting occurred, animals that won or lost an aggressive encounter showed significantly greater accessory sex organ development. While circulating T is required for the initiation and maintenance of intermale aggression, it is apparent that additional factors are related to the onset of fighting and the establishment of dominance/ subordinance relationships in mice.     

Neonatal buspirone modulates the intermale aggression in adult mice

Mice of two strains with different levels of male aggression (RSB and RLB) were subjected to daily injections of 5-HT1A receptor agonist buspirone (25 microg) on the 2nd - 6th postnatal days. This neonatal treatment augmented the aggressive behavior (tested in the dyadic contests with non-aggressive A/Sn males) in aggressive RSB mice and reduced aggression in less aggressive RLB. Correlations with different signs were found between the 5-HT and 5-HIAA levels in the neocortex, hippocampus, and hypothalamus and behavioral indices of aggression in RSB and RLB males. The remote effects of neonatal buspirone in these two mice strains presumably depend on genotype-related features of ontogeny of the 5-HT system.     

Effect of chronic castration on testosterone and estrogen binding to mouse kidney

The effects of prolonged castration on cytosol and nuclear androgen binding were studied in an attempt to explain the apparent resistance to androgen action observed in chronic castrates of various species. The mouse kidney was chosen for study because it is an androgen responsive tissue, extensively characterized, which does not atrophy following castration. Presence of estradiol receptors in the same tissue permitted us to compare the effects of castration on androgen and estrogen binding.Specific nuclear uptake of [³H]-testosterone was not different in kidney minces from 24 h, 1 week and 2 week castrate male mice. Four and 6 weeks after castration, however, a 2-fold increase in the number of available cytosol testosterone binding sites was observed. No changes in estrogen binding were found in chronically castrated male mice. Treatment with the nonaromatizable androgen, dihydrotestosterone, prevented these changes in androgen binding, whereas treatment with estradiol did not.These data indicate that androgen exposure is important in the regulation of androgen receptor activity in male mouse kidney. Whether the differences observed in prolonged castrates result from changes in receptor synthesis, processing or metabolism remains to be determined.     

Context-dependent effects of castration and testosterone treatment on song in male European starlings

Most seasonally breeding songbirds display dramatic seasonal fluctuations in plasma testosterone (T) levels and mate attraction behaviors, including song. However, males of some songbird species, such as the European starling (Sturnus vulgaris), continue to sing at high levels after the breeding season, when T levels are basal. In male starlings song during the breeding season functions mainly to attract mates, whereas song during the nonbreeding season appears unrelated to reproduction. This suggests that song produced in a context unrelated to female courtship, unlike song directed toward females, is not regulated by plasma T. In captive males housed in large outdoor aviaries we explored the relationship between plasma T and song produced during the breeding season within and outside a courtship context. This was achieved by determining the effects of castration and subsequent T treatment on song and mate attraction behaviors in both the presence and the absence of a female. Compared to intact males, castrated males did not show reduced song activity in the absence of a female for at least 6 months after the operation, strongly suggesting that the expression of noncourtship song is not regulated by plasma T. Likewise, we found that experimentally elevating T levels in castrated males did not affect noncourtship song rates. However, control castrated males receiving empty implants tended to show reduced noncourtship song rates after implantation. This may have been due to a suppressive effect caused by the presence of the T-implanted castrated males in the same aviary. In contrast, courtship singing was clearly controlled by plasma T: it was abolished by castration and restored by subsequent T replacement when males were housed both individually and in a group situation. High plasma levels of T also appeared necessary for the activation of three other behavioral traits critical for mate attraction, namely, nesthole occupancy, spending time (singing) in a nesthole, and carrying green nesting material into a nesthole.     

Adrenomedullary hormonal stimulation and hyperglycemia following intermale aggression in the bandicoot rat

The aim of the present investigation is to evaluate adrenomedullary hormones and blood glucose responses to intermale aggression in the bandicoot rat. Aggression elicited a rise in adrenaline and noradrenaline content of the adrenal gland and in blood glucose level in the subordinate rats. No significant change was marked in the dominant rats after aggression. It is suggested that during aggression the subordinate rats suffered from psychosomatic stress that resulted in hyperactivity of the adrenal medulla and consequently hyperglycemia.     

A quantitative trait locus on chromosome 1 modulates intermale aggression in mice

Aggression between male conspecifics is a complex social behavior that is likely modulated by multiple gene variants. In this study, the BXD recombinant inbred mouse strains (RIS) were used to map quantitative trait loci (QTLs) underlying behaviors associated with intermale aggression. Four hundred and fifty‐seven males from 55 strains (including the parentals) were observed at an age of 13 ± 1 week in a resident‐intruder test following 10 days of isolation. Attack latency was measured directly within a 10‐minute time period and the test was repeated 24 hours later. The variables we analyzed were the proportion of attacking males in a given strain as well as the attack latency (on days 1 and 2, and both days combined). On day 1, 29% of males attacked, and this increased to 37% on day 2. Large strain differences were obtained for all measures of aggression, indicating substantial heritability (intraclass correlations 0.10‐0.18). We identified a significant QTL on chromosome (Chr) 1 and suggestive QTLs on mouse Chrs 1 and 12 for both attack and latency variables. The significant Chr 1 locus maps to a gene‐sparse region between 82 and 88.5 Mb with the C57BL/6J allele increasing aggression and explaining about 18% of the variance. The most likely candidate gene modulating this trait is Htr2b which encodes the serotonin 2B receptor and has been implicated in aggressive and impulsive behavior in mice, humans and other species.     

The subcellular localization of the changes in ribonuclease and phosphatase activities of the mouse kidney produced by castration and testosterone

Male mice were castrated at 2 months of age and a pellet of testosterone propionate was implanted subcutaneously ten days later. After 14 days, normal, castrated and androgen treated mice were autopsied simultaneously. The kidneys of each group were homogenized, pooled and fractionated by centrifugation into the various subcellular components. The alkaline ribonuclease and phosphatase activities were localized in the microsomal fraction and changed in inverse relationship to the previously observed changes in the rate of protein biosynthesis and the concentration of microsomal and polysomal RNA induced by castration and androgen administration. Esterase activity also was localized in the microsomal fraction and its specific activity decreased after castration and was restored to normal by testosterone. The activities of acid ribonuclease, acid phosphatase and the several marker enzymes (glucose-6-phosphatase, nucleotidase, succinic dehydrogenase and glucose-6-phosphate dehydrogenase) changed in direct proportion to the changes in weight of the kidney after castration and androgen stimulation.     

Effect of castration and administration of testosterone on cytosol and nuclear androgen receptor in mouse submandibular gland

The effect of castration or administration of testosterone propionate on the subcellular distribution of androgen receptor in mouse submandibular gland was investigated. Within 10 h after castration of male mice, most of the androgen receptor in nuclei was significantly reduced, the androgen receptor in cytosol increased and the increased cytosol receptor retained for at least 40 h. A single injection of testosterone propionate to female mice resulted in the translocation of cytosol androgen receptor to the nuclei by 30 min. The nuclear receptor level remained for at least 24 h and the cytosol receptor was replenished by 24-72 h. These results reveal that the endocrine manipulations such as castration and testosterone injection cause the change in the subcellular distribution of androgen receptor from mouse submandibular gland in both sexes.     

The effects of competition and implicit power motive on men's testosterone,emotion recognition,and aggression

A contribution to a special issue on Hormones and Human Competition.We investigated the effects of competition on men's testosterone levels and assessed whether androgen reactivity was associated with subsequent emotion recognition and reactive and proactive aggression. We also explored whether personalized power (p Power) moderated these relationships. In Study 1, 84 males competed on a number tracing task and interpreted emotions from facial expressions. In Study 2, 72 males competed on the same task and were assessed on proactive and reactive aggression. In both studies, contrary to the biosocial model of status (Mazur, 1985), winners' testosterone levels decreased significantly while losers' levels increased, albeit not significantly. Personalized power moderated the effect of competition outcome on testosterone change in both studies. Using the aggregate sample, we found that the effect of decreased testosterone levels among winners (compared to losers) was significant for individuals low in p Power but not for those with medium or high p Power. Testosterone change was positively related to emotion recognition, but unrelated to either aggression subtype. The testosterone-mediated relationship between winning and losing and emotion recognition was moderated by p Power. In addition, p Power moderated the direct (i.e., non-testosterone mediated) path between competition outcome and emotion recognition and both types of aggression: high p-Power winners were more accurate at deciphering others' emotions than high p-Power losers. Finally, among high p-Power men, winners aggressed more proactively than losers, whereas losers aggressed more reactively than winners. Collectively, these studies highlight the importance of implicit power motivation in modulating hormonal, cognitive, and behavioral outcomes arising from human competition.     

Effect of castration on hypothalamic testosterone metabolism in the male rat

In vitro studies were performed of hypothalamic testosterone (T) metabolism 30 days after castration of adult male rats. No changes were seen in T conversion into dihydrotesterone and estrogens in the castrated rats. Plasma T levels were decreased while plasma estradiol concentrations did not differ from those of intact controls. It was suggested that the hypothalamic T metabolism probably is not androgen dependent.     

Tissue-specific effects of testosterone on S-adenosylmethionine formation and utilization in the mouse.

Exogenous administration of testosterone produced several metabolic tissue-specific changes in female mouse kidneys, but not in the liver. The hormone induced ornithine decarboxylase (ODC) activity, and also profoundly influenced metabolism of S-adenosylmethionine (AdoMet). Therefore, the activity of the AdoMet-synthesizing enzyme (AdoMet synthetase) and of cystathionine synthase, which commits homocysteine irreversibly to the transsulfuration pathway, were significantly increased. In contrast to the level of AdoMet in the liver the renal level of this metabolite was augmented, whereas the level of S-adenosylhomocysteine (AdoHcy) did not change. This resulted in an increase of the AdoMet/AdoHcy ratio. In testosterone-treated mice, pulse-labelled with [methyl-14C]methionine, the radioactivity recovered in the kidneys doubled, but in the liver remained the same. The rise in radioactivity recovered occurred mainly in TCA-soluble compounds and lipids, and to a smaller extent, in proteins and nucleic acids.