Critical exposure time for androgen activation of male sexual behavior in rats

Abstract

We determined the minimum number of hours per day of testosterone (T) exposure required to activate male sexual behavior, and correlated these changes with the temporal parameters of androgen receptor occupation. For the first part of the study, castrated Long-Evans male rats received two 10 mm T-filled Silastic capsules in open flank pouches for 4, 8, 12, 16, 18, 21, or 24 hours per day over a 10 day period. Tests for male sexual behavior were conducted on days 2–3, 4–5, 7–8, and 9–10 of T treatment. A significantly higher proportion of males receiving 21 or 24 hr of daily T exposure mounted, intromitted and ejaculated compared to groups with daily T exposures of 18 hr or less. In the second part of this study we assessed whether it was necessary to maintain high levels of androgen receptor occupation during the 21–24 hr exposure period in order to activate male sexual behavior. Cell nuclear androgen receptor occupation was measured in HPAS (combined hypothalamus, preoptic area, amygdala and septum) of rats receiving 12, 21, or 24 hr of T exposure. In all three groups, nuclear androgen receptor occupation was high at the time of capsule removal, and fell significantly by 3 hr following T capsule removal. By 6 hr after T capsule removal, androgen receptor binding had fallen to castrate levels. These results demonstrate that, although relatively brief (≤18 hr/day) exposures to testosterone can activate mounts and intromissions, significantly more responses are found in males receiving at least 21 hr of T exposure per day. Moreover, prolonged daily exposure to testosterone (at least 21 hours per day) is necessary for the elicitation of ejaculation. It is suggested that 21 hr of T exposure per day may be a critical exposure time, below which androgen receptor occupation cannot be sustained at levels adequate to activate male sexual behavior. These data support a role for neural androgen receptor occupation and genomically mediated alterations in protein synthesis in activating male rat sexual behavior.