Overexpression of transforming growth factor !a in transgenic mice alters nonreproductive, sex-related behavioral differences: Interaction with gonadal hormones.

Abstract

Sexually dimorphic differences in voluntary sodium intake, locomotor activity, immobility in the swim test, and aggressive behavior were found to be altered in transgenic CD-1 mice that overexpressed transforming growth factor alpha (TGF alpha). In contrast to nontransgenic CD-1 mice, immobility in the swim test was longer and sodium intake higher in the male TGF alpha mice than in the female TGF alpha mice. These findings indicate that the male TGF alpha mice exhibited feminization of some behaviors. Furthermore, the male TGF alpha mice were highly aggressive. Castration reversed the behavioral effects in the adult male transgenic mice, but ovariectomy did not reverse the behavioral effects in the adult female transgenic mice. Thus the feminizing effect of TGF alpha on some nonreproductive behaviors and increased aggressive behavior in male mice may be mediated through an interaction between this growth factor and gonadal hormones.

Maternal High n-6 Polyunsaturated Fatty Acid Intake during Pregnancy Increases Voluntary Alcohol Intake and Hypothalamic Estrogen Receptor Alpha and Beta Levels among Female Offspring

“…For example, absence of ER-· renders the male knockout mice nonaggressive, while aggressiveness in female ER-· knockout mice is increased [12]. These data support findings showing that male and female mice respond in an opposite manner to changes in adult estrogenic exposures [7,13]. Further, absence of ER-ß is linked to increased aggressiveness in male knockout mice and does not change female aggressive behavior [14].…”

“…Aggressive behavior is not altered in female ER-ß knockout mice [14]. Since adult exposure to estrogens is known to induce aggressiveness in male mice and rats, but reduce it in female rodents [7,13], it appears that in both females and males, ER-· in the adult rodent brain is mediating the effects of estrogens on this behavior. Further, activation of ER-ß might suppress aggressiveness in male rodents.…”

“…Thus, a long-lasting increase in the brain ER-ß levels in the female mice exposed to a high n-6 PUFA diet in utero may suggest masculinization of their brain. Further, female mice exhibit higher levels of locomotor activity, spend longer times immobile in the swim test, are less aggressive and consume less alcohol than male mice [13,22]. Changes seen at the behavioral level consisting of a shortened time spent immobile in the swim test [6], increased aggressiveness [6] and increased voluntary alcohol intake in the female offspring of mothers consuming a high n-6 PUFA diet are also indicative of masculinization of their brain.…”

Gene × Environment Effects: Stress and Memory Dysfunctions Caused by Stress and Gonadal Factor Irregularities during Puberty in Control And TGF-α Hypomorphic Mice

“…Gonadectomy of TGF-a transgenic male and female mice cause reduced immobility during Porsolt's swim test, whereas it increased the immobility duration in CD-1 control males (Hilakivi-Clarke, 1994). However, the genotype difference was altered only in males and not in females (Hilakivi-Clarke, 1994). In addition, there are sex-dependent tumor formation differences in TGF-a transgenic mice that suggest gonadal hormone involvement in TGFa-dependent stress regulation (Takagi et al, 1992).…”

Homologous genes, aggression, and animal models

“…'Roubertoux et al, 1994. J Maxson, 1996b'Hilakivi-Clarke, 1994 to wild type. However, homozygotes for three of the seven knockouts (CamK2a, Estr, Hlr) decrease one type of aggressive behavior in male mice.…”