REGULATORY CAPACITY OF AN ANDROGEN-SPECIFIC ENHANCER OF THE MOUSE SLPGENE IN TRANSGENIC MICE

Different steroid hormone receptors can activate transcription from th e same hormone response element (HRE) in vitro, but in vivo the effect s of each hormone on gene activity are distinct. To determine sequence s mediating androgen-specific response in a physiological setting, we placed the androgen-responsive mouse sex-limited protein gene (Sip) en hancer before a tkCAT reporter in transgenic mice. The enhancer contai ns a consensus HRE plus accessory factor binding sites that act in con cert to direct transcription in response to androgen. A 160 bp fragmen t, C'Delta 2, is responsive to several steroids in transfection; in tr ansgenic mice, this enhancer was active in several tissues of male and female mice, in four of six transgenic lines. In striking contrast, C 'Delta 9, a 120 bp sub-fragment of C'Delta 2 that responds only to and rogen in transfection, showed activity in testes, prostate and kidney, where it was strongly androgen-inducible in females. However, express ion was obtained in only one transgenic line. Mullimerization of the C 'Delta 9 enhancer conferred expression in prostate, but again in only one line. The greater penetrance of C'Delta 2 expression was not drive n by glucocorticoids, as adrenalectomy had little effect, but may be d ependent on the NF-kappa B-like element absent from the C'Delta 9 frag ment. That two transgenic lines showed expression in androgen target s ites driven by enhancers that are androgen-specific in vitro suggested that activation of this enhancer, when it could occur, was in respons e to androgen. The dramatically different behavior of the two related enhancer sequences underscores the importance of chromosomal context t o the activity and specificity of regulatory elements. (C) 1997 Elsevi er Science Ireland Ltd.