J Physiol Volume 581, Number 2, 665-678, June 1, 2007 DOI: 10.1113/jphysiol.2007.128728
Postnatal androgen deprivation dissociates the development of smooth muscle innervation from functional neurotransmission in mouse vas deferens
J. A. Brock1,
D. J. Handelsman2 and
J. R. Keast3
1 Prince of Wales Medical Research Institute, University of New South Wales, Randwick, NSW 2031, Australia
2 Anzac Research Institute, University of Sydney, NSW 2139, Australia
3 Pain Management Research Institute, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia
The pelvic autonomic nervous system is a target for circulating androgens in adults, with androgen exposure or deprivation affecting the structure and function of urogenital tract innervation. However, the critical period for androgen exposure to initially establish pelvic autonomic neuromuscular transmission has not been determined. We have examined the sympathetic innervation of the vas deferens in hypogonadal (hpg) mice that are deprived of androgens after birth but undergo normal prenatal sexual differentiation and remain androgen responsive throughout life. In vasa deferentia from hpg mice, purinergic excitatory junction potentials and contractions could not be elicited by electrical stimulation and P2X1 purinoceptors could not be demonstrated by immunofluorescence. Moreover, a novel inhibitory nitrergic transmission developed. Administering testosterone to adult hpg mice restored purinergic excitatory transmission and P2X1 purinoceptor immunofluorescence, and nitrergic inhibitory transmission was lost. Despite the deficit in excitatory neurotransmission in hpg mice, their vasa deferentia were innervated by numerous noradrenergic axons and pelvic ganglia appeared normal. In addition, noradrenergic contractions could be elicited by electrical stimulation. This study has revealed that postnatal androgen exposure has a profound effect on the development of excitatory transmission in vas deferens smooth muscle, primarily by a postjunctional action, but is not essential for development of the structural innervation of this organ. Our results also indicate that there is no postnatal critical period for androgen exposure to establish neuroeffector transmission and that postnatal androgen exposure can be delayed until adulthood, with little consequence for establishment of normal sympathetic neurotransmission.
(Received 21 January 2007;
accepted after revision 16 March 2007;
first published online 22 March 2007)
Corresponding author J. R. Keast: Pain Management Research Institute, Royal North Shore Hospital, St Leonards NSW 2065, Australia. Email: jkeast{at}med.usyd.edu.au
Copyright © 2007 The Physiological Society.