Hormonal regulation of motor unit size and synaptic strength during synapse elimination in the rat levator ani muscle

Abstract

Previous anatomical studies suggest that androgen regulates synapse elimination in the androgen-sensitive levator ani(LA) muscle of the rat. Androgen treatment beginning on postnatal day 7 (P7) prevents some of the normal loss of multiaxonal innervation in this muscle. The present study used physiological techniques to measure the number and size of LA motor units during the synapse elimination period in muscles from normals, and castrates treated with either testosterone propionate or oil. The number of increments in LA twitch tension as nerve stimulation intensity increased, a measure of the number of motor units, was the same at the end (P28) of synapse elimination as near the beginning (P7) of this process. This result indicates that motoneuronal cell death does not contribute to synapse elimination in the LA. Moreover, androgen during this period did not influence the number of LA motor units. In contrast, between P7 and P28, there was a dramatic decline in the size of LA motor units, as indicated by a decrease in the percentage of twitch or tetanus tension of individual motor units relative to the maximal twitch or tetanus tension of the whole muscle. In addition, androgen treatment of castrated males during this period prevented some of the normal decline in the size of LA motor units. Estimates of the number of inputs per LA muscle fiber derived from the number of LA motor units and their average size indicate that androgen maintains polyneuronal innervation in the LA muscle. This finding supports previous anatomical studies suggesting that androgen can prevent synapse elimination in this muscle. The strength of LA synapses was also examined by measuring the tetanus: twitch ratio of individual motor units and by measuring the safety margin of LA synapses. Both measurements indicated that the average strength of LA synapses increases during synapse elimination. Moreover, androgen appeared to spare synapses from elimination without increasing their strength, since androgen-treated muscles generally had larger motor units but the same mean tetanus:twitch ratio and safety margins as untreated LA muscles except at P28, when synapses in androgen-treated LA muscles had appreciably lower safety margins than normal. These results suggest that androgen regulates synapse elimination through a mechanism(s) independent of synaptic strength.

Neuronal Size in the Spinal Nucleus of the Bulbocavernosus: Direct Modulation by Androgen in Rats with Mosaic Androgen Insensitivity

“…Second, muscle fibers are multinucleated cells, and we have never observed a BC/LA muscle fiber in mosaics completely lacking AR-immunoreactive nuclei. Third, each SNB motoneuron innervates, on average, hundreds of muscle fibers (Jordan et al, 1992), and individual BC/LA muscle fibers receive polyneural innervation from the SNB (Jordan et al, 1989), making it unlikely that any SNB motoneuron could fail to be in contact with AR-competent muscle fibers.…”

A sex difference in synaptic efficacy at the laryngeal neuromuscular junction of Xenopus laevis

“…Androgenic steroids are also good candidates for control of synaptic efficacy in adults and have been shown to reduce synaptic efficacy at another androgen-sensitive synapse-on "clasper" muscles-in Xenopus luevis (Nagaya and Herrera, 1991). In the levator ani of developing male rats, results of experiments using muscle twitch tension in depleted calcium saline to estimate synaptic efficacy suggest that androgen lowers synaptic strength at some developmental stages (Jordan et al, 1992).…”

The organizational–activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues

“…In at least one model system, sex steroids can influence the loss of synapses, suggesting a mechanism for selecting specific synapses to be saved as others are lost (Jordan et al, 1992). At the same time, sex steroids are influencing the growth of dendrites permanently, although the permanence of this effect is not yet explained.…”