Hormonal regulation of aggression: Evidence for a relationship among genotype, receptor binding, and behavioral sensitivity to androgen and estrogen

Abstract

Gonadectomized male mice from the CF‐1, CFW, and CD‐1 strains were exposed to different androgens (testosterone, dihydrotestosterone, methyltrienolone) or estrogens (estradiol, diethylstilbestrol) and tested for aggressive behavior. Genetic differences in sensitivity to the aggression‐promoting property of the various treatments were found. CF‐1 mice responded to either androgenic or estrogenic stimulation, CFW males were most sensitive to the estrogen treatments, while CD‐1 males responded to androgen but were relatively insensitive to the aggression‐promoting property of estrogens. These data suggest that there may be multiple aggression‐activating systems and that the functional pathway varies with genotype. Additional experiments examined whether receptor binding in the hypothalamic‐preoptic‐septal region was related to the genetic differences in behavioral responsiveness. The binding data suggested that sensitivity to the aggression‐promoting property of estrogens was related to either a higher concentration of binding sites or to higher affinity binding between estrogen and its receptor. A systematic relationship between dihydrotestosterone binding and behavioral responsiveness to androgen was not found.

Hormonal background of physiological aggressiveness in psychologically healthy women

“…All together, these data do not seem to reveal cycle-related fluctuations of physiological aggressiveness, in accord with the report of Dougherthy et al (1998). This seems to contradict the data from the literature reporting relationships between sexual hormone concentrations, in particular FT and E, and aggressive behavior in women (Jnoff-Gormain et al, 1981;Simon and Whalen, 1986;Olweus et al, 1988;Gladue, 1991;Leibenluft et al, 1994;Gerra et al, 1996Gerra et al, , 1997Gerra et al, , 1998Finkelstein et al, 1997;Aromaki et al, 1999;Van Herringen et al, 2000;Grieng et al, 2001;Thiblin and Parlklo, 2002). However, these data refer to elevated or pathological or provoked aggressiveness related to hormonal secretions or administration, while we investigated the possible hormonal background of fluctuations of normal aggressiveness during the normal menstrual cycles in subjects in resting conditions.…”

“…Also, it is well known that peripherally secreted hormones, including androgens, glucocorticoids and growth hormone and centrally secreted opioids influence the development and the degree of physiological and pathological aggressiveness in experimental animals (Grieng et al, 2001) and in humans (Olweus et al, 1988;Coccaro et al, 1997;Gerra et al, 1996Gerra et al, , 1997Gerra et al, , 1998Finkelstein et al, 1997;Archer et al, 1998;Aromaki et al, 1999;Van Herringen et al, 2000;Pope et al, 2000;Grieng et al, 2001;Thiblin and Parlklo, 2002;O'Connor et al, 2002;Eriksson et al, 2003;Rowe et al, 2004). Little is known about the influence that female sexual hormones exert on this behavioral parameter, even though in experimental animals of both sexes, especially in major primates, aggressive behavior has been linked to variations of prenatal and postnatal estrogen secretions (Simon and Whalen, 1986;Finkelstein et al, 1997;Girolami et al, 1997;Palanza et al, 1999;Toda et al, 2001). Data from humans are sparse and contradictory.…”

The Role of Alcohol and Steroid Hormones in Human Aggression

“…Androgens and estrogens are responsible for most of the observed differences between males and females in brain structure and function (Rubinow and Schmidt, 1996). Estrogen has been related to aggression in animals (Hilakivi-Clarke, 1996;Simon and Whalen, 1986), while human studies on estrogen and aggressive behavior have been more inconclusive (Beatty, 1992). In a study of men suffering from dementiarelated aggression, the subjects receiving transdermatal estradiol treatment decreased their physical and sexual aggressiveness but verbal aggression remained unchanged (Kay et al, 1996).…”

Agonistic behavior in males and females: Effects of an estrogen receptor beta agonist in gonadectomized and gonadally intact mice

“…Aggression research with laboratory rodents has typically focused on males’ behavior, usually employing the resident-intruder test (e.g., Thor and Flannelly, 1976; Brain et al, 1981; Simon and Whalen, 1986), where an intruder is introduced into the home cage of another, usually isolated, animal (the resident). Measures of fighting or overt aggression such as latency to, or frequency of, attack, are taken (e.g., Thor and Flannelly, 1976; Simon and Whalen, 1986; Parmigiani et al, 1999; Morè, 2008), sometimes together with other measures of “agonistic” behavior, which include both the aggression and the reaction to it (Olivier et al, 1989, 1991; Alleva, 1993; Pietropaolo et al, 2004; Branchi et al, 2006). In mice, this paradigm takes advantage of the fact that males will often establish and maintain an exclusive territory or dominate a shared territory under natural conditions (Miczek et al, 2001, 2007; see Latham and Mason, 2004 for a review).…”

“…It has long been known that castration eliminates intermale aggression in wild as well as inbred and outbred laboratory mice (e.g., Uhrich, 1938; Beeman, 1947; Luttge, 1972; Brain and Bowden, 1979; Simon and Whalen, 1986). The administration of prototypical male gonadal hormone, testosterone (T), will restore aggression in these castrated males (Beeman, 1947; Tollman and King, 1956; Luttge, 1972; Brain and Bowden, 1979; Simon and Whalen, 1986). …”