Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system.
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 nonaromatizable 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 5alpha-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.
Verhovshek
Tom
T
Department of Psychological and Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, Indiana 47405, USA.
Buckley
Katherine E
KE
Sergent
Melissa A
MA
Sengelaub
Dale R
DR
D000375:Aging; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D018120:Finasteride / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009919:Orchiectomy; D051381:Rats; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology
D000728:Androgens; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D042944:Cholestenone 5 alpha-Reductase; D017316:Fadrozole