Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor beta knockout (betaERKO) male mice

Estrogen, as an aromatized metabolite of testosterone, has a facilitatory effect on male aggressive behavior in mice. Two subtypes of estrogen receptors, alpha (ER-alpha) and beta (ER-beta), in the brain are known to bind estrogen. Previous studies revealed that the lack of ER-alpha gene severely reduced the induction of male aggressive behavior. In contrast, mice that lacked the ER-beta gene tended to be more aggressive than wild type (WT) control mice, although the behavioral effects of ER-beta gene disruption were dependent on their social experience. These findings lead us to hypothesize that estrogen may facilitate aggression via ER-alpha whereas it may inhibit aggression via ER-beta. In the present study, we further investigated the role of ER-beta in the regulation of aggressive behavior by examining developmental changes starting at the time of first onset, around the age of puberty. Aggressive behaviors of ER-beta gene knockout (betaERKO) mice were examined in three different age groups, puberty, young-adult, and adult. Each mouse was tested every other day for three times in a resident-intruder paradigm against olfactory bulbectomized intruder mice and their trunk blood was collected for measurements of serum testosterone after the completion of the study. Overall, betaERKO mice were significantly more aggressive than WT. These genotype differences were more pronounced in puberty and young adult age groups, but not apparent in the adult age group, in which betaERKO mice were less aggressive than those in two younger age groups. Serum testosterone levels of betaERKO mice were significantly higher than those of WT mice only in the pubertal age group, but not in young adult (when betaERKO mice were still significantly more aggressive than WT mice) and adult (when no genotype differences in aggression were found) age groups. These results suggest that ER-beta mediated actions of gonadal steroids may more profoundly be involved in the inhibitory regulation of aggressive behavior in pubertal and young adult mice.     

Photoperiod and testosterone independently affect vocal control region volumes in adolescent male songbirds

Previously, we found that, unlike adults, adolescent male dark-eyed juncos (Junco hyemalis) maintained large Area X volumes despite having low plasma testosterone concentrations. Other studies indicate that photoperiod may act independently of testosterone to modulate vocal control region (VCR) volumes in adult songbirds. In the present study, we investigated the effects of testosterone and photoperiod on the volumes of four VCRs in adolescent male juncos. To test the hypothesis that VCR volumes in these males are testosterone independent, we treated birds exposed to short days with testosterone and later compared their VCR volumes with those of birds exposed to short days without testosterone. To examine whether photoperiod alone could affect VCR volumes independent of testosterone, we measured these volumes in photorefractory birds exposed to long photoperiod without testosterone. Administering testosterone induced singing, yet increased the volume of only one VCR, the robust nucleus of the anterior neostriatum (RA). In contrast, long photoperiod increased several VCR volumes (Area X, higher vocal center, and RA) despite low testosterone levels, but did not induce singing. Our results suggest a limited role for testosterone, but an important role for photoperiod, in controlling VCR volumes in adolescent male juncos. In addition, the results demonstrate that singing behavior can be induced in adolescent males without a concomitant increase in most VCR volumes. © 1998 John Wiley & Sons, Inc. J Neurobiol 36: 550–558, 1998     

The therapeutic use of androgens in women

Androgens have significant and varied actions in women and there is now acknowledgment that women may experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent androgen replacement can be effective in relieving both the physical and psychological symptoms of androgen insufficiency, and is indicated for clinically affected women. Testosterone replacement for women is now available in a variety of formulations. It appears to be safe, with the caveat that doses are restricted to the ‘therapeutic’ window for androgen replacement in women, such that the beneficial effects on wellbeing and quality of life are achieved without incurring undesirable virilizing side effects.

The predominant symptom of women with androgen deficiency is loss of sexual desire. This is not limited to women experiencing a surgical menopause but may also be a feature of women who have either undergone premature or natural menopause. There is increasing interest in other uses of androgen replacement in women that include premenopausal iatrogenic androgen deficiency states, glucocorticosteroid-induced bone loss, management of wasting syndromes and possibly premenopausal bone loss, premenopausal loss of libido and the treatment of the premenstrual syndrome.     

Androgen receptor gene sequence and basal cortisol concentrations predict men's hormonal responses to potential mates

Exposure to potential mates triggers rapid elevations of testosterone and glucocorticoid concentrations in males of many non-human species, and preliminary studies support similar effects in human males. The human studies have all reported large individual differences in these responses, however, and the present study tested whether specific biological variables may help explain these differences. Replicating past research, the present study found that men''s salivary testosterone and cortisol concentrations increased after a brief conversation with a young woman, but did not change (or slightly decreased) after a conversation with a young man. In addition, smaller numbers of CAG repeats in men''s androgen receptor gene, and lower baseline cortisol concentrations, each predicted larger testosterone responses to the interactions with women. The CAG repeat finding demonstrates that a specific genetic polymorphism predicts physiological responses to social interactions that may in turn have important downstream consequences on men''s mating behaviour. The effects of cortisol are consistent with past demonstrations of glucocorticoid inhibition of testosterone production and show that such inhibition also affects testosterone responses to social stimuli. In sum, the present study both confirms men''s hormonal reactions to potential mates and identifies novel biological variables that predict individual differences in these responses.