Quantitative study of the effects of denervation and castration on the levator ani muscle of the rat

The levator ani muscle (LA) of the rat is highly androgen-sensitive and, like all skeletal muscles, deteriorates structurally and functionally when denervated. In order to elucidate the interplay of neural and endocrine influences, the separate and combined effects of denervation and castration on myofiber cross-sectional area and nuclear populations were quantitatively studied. In one group of 4-month-old male rats (A), the LA was denervated. Another group (B) was surgically castrated and a third group (C) was both denervated and castrated. The control rats (D) remained both gonad- and nerve-intact. After two months, the LA was obtained for myofiber and nuclear enumeration, cross-sectional area and satellite cell frequency determination. In the denervated muscle of gonad-intact rats (Group A), myofiber cross-sectional area was markedly diminished (265.84+/-11.38 microm2; compared with controls [Group D]: 1519.98+/-79.41 microm2; P < 0.05). Satellite cell nuclei, as a percentage of total sublaminar nuclei (i.e., satellite cell ratio), increased significantly (4.26%, from a control value of 1.91%). Castration alone (Group B) resulted in pronounced myofiber atrophy (mean cross-sectional area: 754.03+/-89.63 microm2) but had no significant effect on satellite cell ratio (2.36%). The combination of castration and denervation (Group C) elicited the same degree of myofiber atrophy as denervation alone (Group A) but had no significant impact on satellite cell ratio. Instead, the nuclear count per myofiber declined to about a third of the control level (300.5+/-38.49 compared with 861.7+/-24.8; P < 0.05). The results indicate that the atrophic effects of denervation and castration on the LA are non-synergistic and mechanistically similar. They also show that the inability of satellite cells to respond mitotically to the withdrawal of neural input under disandrogenized conditions is a factor in the myonuclear depletion of the denervated muscle of castrated rats.