Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system

Abstract

The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Androgens are necessary for the development of the SNB neuromuscular system, and in adulthood, continue to influence the morphology and function of the motoneurons and their target musculature. However, estrogens are also involved in the development of the SNB system, and are capable of maintaining function in adulthood. In this experiment we assessed the ability of testosterone metabolites, estrogens and non-aromatizable androgens, to maintain neuromuscular morphology in adulthood. Motoneuron and muscle morphology was assessed in adult normal males, sham-castrated males, castrated males treated with testosterone, dihydrotestosterone, estradiol, or left untreated, and gonadally intact males treated with the 5α-reductase inhibitor finasteride or the aromatase inhibitor fadrozole. After 6 weeks of treatment, SNB motoneurons were retrogradely labeled with cholera toxin-HRP and reconstructed in three dimensions. Castration resulted in reductions in SNB target muscle size, soma size, and dendritic morphology. Testosterone treatment after castration maintained SNB soma size, dendritic morphology, and elevated target muscle size; dihydrotestosterone treatment also maintained SNB dendritic length, but was less effective than testosterone in maintaining both SNB soma size and target muscle weight. Treatment of intact males with finasteride or fadrozole did not alter the morphology of SNB motoneurons or their target muscles. In contrast, estradiol treatment was completely ineffective in preventing castration-induced atrophy of the SNB neuromuscular system. Together, these results suggest that the maintenance of adult motoneuron or muscle morphology is strictly mediated by androgens.

Denervation and Castration Effects on the Cross‐Sectional Area of Pubococcygeus Muscle Fibers in Male Rats

“…We found that castration had a greater effect than denervation, that is, castration presented a lack of ranges in the cross-sectional area distribution from 2,000 to 3,999 lm 2 , while in denervation it was from 2,500 to 3,999 lm 2 . In relation to our findings, it seems that other than the reduction from a direct hormonal effect on the muscle fibers, castration reduces the indirect effect on the neuromuscular complex (Monks et al, 2004;Verhovshek et al, 2010) resulting in a reduction of the Pcm reflex activity, similar to that described in the bulbocavernosus muscle (Hart, 1967;Davidson et al, 1978). In contrast, denervation produced a lesser effect because denervation itself does not prevent the direct and indirect action of gonadal hormones on the Pcm fibers.…”

“…Gonadal hormones also influence skeletal muscle morphology through a direct and indirect action on muscle fibers (Rand and Breedlove, 1992;Herbst and Bhasin, 2004;Verhovshek et al, 2010). Interestingly, denervation affects all striated muscles while castration does not, for example, plantaris is not sensitive to changes in gonadal hormone levels (Antonio et al, 1999).…”

Aromatase expression is linked to estrogenic sensitivity of periurethral muscles in female rabbits

“…It may be possible that a reduced aromatase expression in both OVX and OVX + EB groups could lead to an elevated concentration of androgens in the Bsm maintaining the Bsm morphometry similar to control rabbits as required for androgen‐dependent muscles of mice . Apart from the muscle morphometry, the impact that steroids synthesized in the Pcm and Bsm have on motoneurons innervating them should be further analysed …”

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain

“…Difference in dendritic branching and soma size of spinal nucleus bulbocavernosus is maintained by testosterone in males 140 …”