Catecholamines are required for the acquisition of secretory responsiveness by sweat glands

The sympathetic innervation of sweat glands undergoes a developmental chang e in transmitter phenotype from catecholaminergic to cholinergic. Acetylcho line elicits sweating and is necessary for development and maintenance of s ecretory responsiveness, the ability of glands to produce sweat after nerve stimulation or agonist administration. To determine whether catecholamines play a role in the development or function of this system, we examined the onset of secretory responsiveness in two transgenic mouse lines, one albin o and the other pigmented, that lack tyrosine hydroxylase (TH), the rate-li miting enzyme in catecholamine synthesis. Although both lines lack TH, thei r catecholamine levels differ because tyrosinase in pigmented mice serves a s an alternative source for catecholamine synthesis (Rios et al., 1999). At postnatal day 21 (P21), 28 glands on average are active in interdigital hi nd footpads of albino TH wild-type mice. In contrast, fewer than one gland is active in albino TH null mice, which lack catecholamines in gland innerv ation. Treatment of albino TH null mice with DOPA, a catecholamine precurso r, from P11 to P21 increases the number of active glands to 14. Pigmented T H null mice, which have faint catecholamine fluorescence in the developing gland innervation, possess 12 active glands at P21, indicating that catecho lamines made via tyrosinase, albeit reduced from wild-type levels, support development of responsiveness. Gland formation and the appearance of cholin ergic markers occur normally in albino TH null mice, suggesting that catech olamines act directly on gland cells to trigger their final differentiation and to induce responsiveness. Thus, catecholamines, like acetylcholine, ar e essential for the development of secretory responsiveness.