Testosterone and aggression: Berthold, birds and beyond

Abstract

Berthold's classic study of domesticated roosters in 1849 demonstrated that testicular secretions are necessary for the normal expression of aggressive behaviour. Although this conclusion is undoubtedly correct, field studies of wild songbirds have yielded important modifications and limitations of Berthold's original hypothesis. For example, studies of the North American song sparrow (Melospiza melodia) during the breeding season reveal that not only does testosterone increase aggression, but aggressive interactions also increase plasma testosterone levels. Furthermore, in winter, nonbreeding song sparrows have low plasma testosterone levels but are very aggressive, and castration of nonbreeding song sparrows does not decrease aggression. Interestingly, an aromatase inhibitor (fadrozole) does decrease male aggression in the nonbreeding season, and the effects of fadrozole can be rescued with oestradiol. In winter, dehydroepiandrosterone (DHEA) from the periphery can be metabolised within the brain to supply oestradiol to specific neural circuits. Additionally, oestradiol might be synthesised de novo from cholesterol entirely within the brain. These mechanisms may have evolved to avoid the 'costs' of circulating testosterone in the nonbreeding season. Recent studies in tropical birds, hamsters, and humans suggest that these neuroendocrine mechanisms are important for the control of aggression in many vertebrate species.

Fig. 1

Effects of the aromatase inhibitor fadrozole (FAD) and 17β-oestradiol (E₂) on territorial aggression of nonbreeding male song sparrows in the field. Males were challenged with a simulated territorial intrusion (STI, live decoy and song playback) for 10 min. Singing (A), rapid flights (B), close approaches (C), and time spent near the decoy (D) are typical aggressive responses in this species. Sample sizes are in parentheses, and asterisks indicate significant differences between groups. Redrawn from data in (44).

Fig. 2

Brain aromatase mRNA expression in a wild male song sparrow. (A) Aromatase mRNA in the bed nucleus of the stria terminalis (BnST), pre-optic area (POA), ventromedial nucleus (VMN) and near the lateral ventricle (v). (B) More caudally, high expression of aromatase mRNA in caudomedial nidopallium (NCM) and nucleus taeniae of the amygdala (Tn), and low expression in hippocampus (HP). A few cells in caudomedial HVC expressed aromatase. Modified from (39).

Fig. 3

(A) A simplified diagram of sex steroid synthesis. Steroids: PREG, pregnenolone; PROG, progesterone; DHEA, dehydroepiandrosterone; AE, androstenedione; T, testosterone; E₁, oestrone; E₂, 17β-oestradiol. Enzymes: P450scc, Cytochrome P450 side chain cleavage; P450c17, Cytochrome P450 17α-hydroxylase/C17, 20 lyase; 3β-HSD, 3β-hydroxysteroid dehydrogenase/isomerase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; Aromatase, Cytochrome P450 aromatase. (B) Levels of dehydroepiandrosterone (DHEA), testoterone, and E₂ (ng/ml) in brachial plasma from wild male song sparrows in the nonbreeding season. Redrawn from data in (40).

Fig. 4

(A) Correlation between plasma dehydroepiandrosterone (DHEA) levels (pg/ml) and Fos immunoreactive (ir) nuclei in the medial bed nucleus of the stria terminalis (BnST). Redrawn from data in (56). (B) Correlation between plasma DHEA levels (pg/ml) and the number of arginine vasotocin (AVT)-ir neurones in the medial BnST. AVT-ir neurone counts are shown as the number of neurones per 40-μm coronal section. For both (A) and (B), subjects received one of three treatments: control (n = 6), YM116 (a DHEA synthesis inhibitor) (n = 4), or YM116 + DHEA (n = 6).

Fig. 5

In vitro metabolism of [³H]-dehydroepiandrosterone (DHEA) to (A) [³H]-androstenedione (AE) and (B) [³H]-oestrogens (E) by zebra finch brain homogenates. (A) Metabolism of [³H]-DHEA to [³H]-AE was abolished by trilostane, a 3β-HSD inhibitor. (B) Metabolism of [³H]-DHEA to [³H]-E was greatly reduced by fadrozole, an aromatase inhibitor. Similar data were obtained using song sparrow brain homogenates. Modified from (58).

Fig. 6

Actions and costs of high circulating testosterone in the breeding season and nonbreeding season. Actions are in black, and potential costs are in red. In the breeding season, a major cost of high circulating testosterone is interference with parental care. In the nonbreeding season, interference with parental care is not an issue, but a major cost of high circulating testosterone is increased energy expenditure. Modified from (13).

Fig. 7

Pathways by which steroids could affect aggression. (A) Gonadal testosterone (T) acts directly on the brain; (B) gonadal T is converted locally to 17β-oestradiol (E₂); (C) adrenal DHEA is converted locally to T and/or E₂; (D) neurosteroids are produced locally in the absence of gonadal and adrenal steroid production. Modified from (6).