Rapid effects of aromatase inhibition on male reproductive behaviors in Japanese quail

Abstract

Non-genomic effects of steroid hormones on cell physiology have been reported in the brain. However, relatively little is known about the behavioral significance of these actions. Male sexual behavior is activated by testosterone partly through its conversion to estradiol via the enzyme aromatase in the preoptic area (POA). Brain aromatase activity (AA) changes rapidly which might in turn be important for the rapid regulation of behavior. Here, acute effects of Vorozole ™ , an aromatase inhibitor, injected IP at different doses and times before testing (between 15 and 60 min), were assessed on male sexual behavior in quail. To limit the risk of committing both types of statistical errors (I and II), data of all experiments were entered into a meta-analysis. Vorozole ™ significantly inhibited mount attempts (p<0.05, size effect [g]=0.527) and increased the latency to first copulation (p<0.05, g=0.251). The treatment had no effect on the other measures of copulatory behavior. Vorozole ™ also inhibited appetitive sexual behavior measured by the social proximity response (p<0.05, g=0.534) or rhythmic cloacal sphincter movements (p<0.001, g=0.408). Behavioral inhibitions always reached a maximum at 30 min. Another aromatase inhibitor, androstatrienedione, induced a similar rapid inhibition of sphincter movements. Radioenzyme assays demonstrated that within 30 min Vorozole ™ had reached the POA and completely blocked AA measured in homogenates. When added to the extracellular milieu, Vorozole ™ also blocked within 5 min the AA in POA explants maintained in vitro. Together, these data demonstrate that aromatase inhibition rapidly decreases both consummatory and appetitive aspects of male sexual behavior.

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

“…Accordingly, in recent experiments conducted in quail, systemic injections of a large dose of Vorozole™, a non-steroidal aromatase inhibitor, significantly reduced most aspects of male copulatory behavior in sexually active males (gonadally intact males or castrates implanted with 40 mm testosterone capsules). Maximal effects were observed after 30 or 45 minutes [67]. The acute effect of aromatase inhibition was even more pronounced on the expression of appetitive male sexual behavior.…”

“…Androstatrienedione (ATD), another unrelated aromatase inhibitor with a very different chemical structure, induced a similar rapid inhibition of RCSM [67]. These behavioral inhibitions correlated with inhibitions of the aromatase activity measured in the preoptic-hypothalamus area (see [67] for further details). The fact that similar effects of aromatase inhibition were observed in gonadally intact males and in castrates chronically treated with testosterone suggests that the behavioral effect resulted from a rapid modulation of aromatase activity and thus local estrogen bioavailability rather than from a rapid change in secretion of gonadal testosterone.…”

“…The behavior returned to a normal rate on the next day [67]. Androstatrienedione (ATD), another unrelated aromatase inhibitor with a very different chemical structure, induced a similar rapid inhibition of RCSM [67]. These behavioral inhibitions correlated with inhibitions of the aromatase activity measured in the preoptic-hypothalamus area (see [67] for further details).…”

“…A significant inhibition of RCSM was observed 30 or 45 min after the injection of Vorozole™ and was no longer significant after 60 min. The behavior returned to a normal rate on the next day [67]. Androstatrienedione (ATD), another unrelated aromatase inhibitor with a very different chemical structure, induced a similar rapid inhibition of RCSM [67].…”

Recent advances in behavioral neuroendocrinology: Insights from studies on birds

“…Both appetitive and consummatory sexual behavior are T-dependent in quail and require the aromatization of T to E 2 , and the POM is an essential target for the activation of behavior (e.g., Riters et al, 1998; for reviews, see Panzica et al, 1996;Balthazart et al, 2004). In addition, recent studies show that pharmacological blockade of aromatase activity produces deficits in both appetitive and consummatory sexual behavior within 15-45 minutes (Cornil et al, 2003; also see Ball and Balthazart, 2004;Balthazart et al, 2004).…”