It is all About the Chase: Neurosteroidogenesis in Male Rats is Driven by Control of Mating Pace

Abstract

Background: Masculine sexual behaviors are dependent on androstane-derived steroids; however, the modulatory effects of mating, and of mating control, on androstane neurosteroidogenesis remain largely unknown.

Objective: Herein, we investigated the effects of mating control, prior sexual experience, and age on brain region specific neurosteroidogenic responses in male rats.

Methods: Effects of acute sexual experience were tested in naïve male rats that either remained sexually- naïve, were exposed to a standard mating chamber, or were either given control of the mating pace in a standard mating chamber (male control) or mated wherein the female stimulus rat controlled the mating pace in a paced-mating chamber (female control). Aged (10-12 months) sexually responsive male rats were similarly euthanized from the homecage or engaged in male controlled or female controlled mating. All rats were euthanized immediately following exposure conditions for radioimmunoassay of steroids in midbrain, hypothalamus, hippocampus and cortex.

Results: Consummatory sexual behavior in male vs. female-controlled mating paradigms was altered by age and prior sexual experience. Male-controlled mating increased androstane neurosteroid metabolism, such that complementary increases in the testosterone (T) metabolite 5α-androstane-3α-17β- diol (3α-diol) in the midbrain and hypothalamus of male rats corresponded to decreases in the prohormone, T. 3α-diol were increased in the hippocampus in response to the context alone, and to a lesser degree in response to mating. Mating diminished neurosteroidogenesis in the cortex. Neurosteroidogenesis was overall reduced in aged male rats compared to naïve controls, however, these effects were more prominent in sexually non-responsive aged male rats.

Conclusion: Extending previous findings, these results indicate differential production of androstane neurosteroids in a mating exposure, age and brain region dependent manner.

Keywords: 5α-androstane-3α-17β-diol (3α-diol); Mating; aging; estradiol; paced-mating; testosterone.

Fig. (1)

Age and prior sexual experience influence sexual performance in female-controlled (paced) compared to male-controlled (standard) mating. Rats were naïve adult males with no prior sexual experience, adult males with one week of sexual experience, or mid-aged (10-12 months old) sexually responsive to a female, or sexually non-responsive to a female. (A) Latencies to mount in female-controlled mating decreased with age and prior sexual experience. (B) Age, and mating control interacted to influence the frequency of sexual contacts. (C) Proportions of ejaculations observed in each testing condition. As each mating session examined a singular ejaculatory series, statistics on the frequency of ejaculation were not performed. * indicates p < 0.05 in post-hoc t-tests comparing sexual responsivity to naïve controls within mating condition.

Fig. (2)

Male-controlled (Standard) mating compared to female-controlled (paced) mating or no mating increased T and 3α-diol in the midbrain, and decreased T and 3α-diol in the hypothalamus of naïve rats. Rats were naïve adult males with no prior sexual experience euthanized from the homecage (no exposure, NE), following 15-min exposure to the standard mating chamber (chamber exposed, CE), following 15-min of female-controlled (paced) mating with a sexually responsive female conspecific (Female-Controlled), or following 15-min of male-controlled (standard) mating with a sexually responsive female conspecific (Male-Controlled). (A-D) 3α-diol. (E-H) E₂ in the midbrain (E), hypothalamus (F), hippocampus (G) and cortex (H). (I-L) T in the midbrain (I), hypothalamus (J), hippocampus (K), and cortex (L). (M) Relative metabolism of androgens. *indicates significant differences using post-hoc t tests from non-mated (NE and/or CE) controls (p < 0.05). **indicates significant post-hoc f-test differences from all other conditions (p < 0.05).

Fig. (3)

Effects of Aging and Sexual Proclivity on Neurosteroidogenesis. Rats were naïve adult males with no prior sexual experience (Naïve), adult males with one week of sexual experience (adult sexually-responsive, SR), or mid-aged (10-12 months old) sexually responsive to a female (mid-aged sexually-responsive (ASR), or sexually non-responsive to a female (mid-aged sexually non-responsive, ASNR). All rats were euthanized directly from the homecage. (A-D) 3α-diol. (E-H) E₂ in the midbrain (E), hypothalamus (F), hippocampus (G) and cortex (H). (I-L) T in the midbrain (I), hypothalamus (J), hippocampus (K), and cortex (L). (M) Relative metabolism of androgens. *indicates significant differences using post-hoc t-tests from naïve controls (p < 0.05). **indicates significant differences using post-hoc f-tests from all other mating conditions. $ indicates significant differences from mid-aged sexually non-responsive males only.

Fig. (4)

Effects of Mating Condition on Neurosteroidogenesis in Mid-Aged Male Rats. Rats were mid-aged sexually-responsive adult males, and euthanized from the homecage (no exposure, NE), following 15-min exposure to the standard mating chamber (chamber exposed, CE), following 15-min of female-controlled (paced) mating with a sexually responsive female conspecific (Female-Controlled), or following 15-min of male-controlled (standard) mating with a sexually responsive female conspecific (Male-Controlled). (A-D) 3α-diol. (E-H) E₂ in the midbrain (E), hypothalamus (F), hippocampus (G) and cortex (H). (I-L) T in the midbrain (I), hypothalamus (J), hippocampus (K), and cortex (L).” (M) Relative metabolism of androgens. *indicates significant differences using post-hoc t tests from no exposure and/or chamber exposed controls (p < 0.05).