The lysosomal membrane complex. Focal point of primary steroid hormone action

Abstract

At short intervals after the intravenous administration of oestradiol-17β, diethylstilboestrol, testosterone or saline control solution to ovariectomized rats, highly purified lysosome samples were prepared in substantial yield from preputial glands, sex accessory organs rich in these organelles. The preparations were essentially devoid of mitochondrial contamination. Exposure in vivo to doses of these hormones varying from 0.1 to 5μg/100g body wt. provoked dose-dependent labilization of the lysosomal membrane surface, as evidenced by significantly diminished structural latency of several characteristic acid hydrolases, including acid phosphatase, β-glucuronidase and acid ribonuclease II, when such preparations were subsequently challenged in vitro with autolytic conditions, detergent or mechanical stress. Enhanced lytic susceptibility induced by hormone pretreatment was occasionally detectable in the initial preparation without further provocative stimuli in vitro. Comparable results were obtained with the corresponding fractions of uterus, despite the more limited concentration of lysosomes in this steroidal target organ. By the present criteria oestradiol-17α was essentially inert, even in a dose 25 times that effective for its active β-epimer (<0.1μg/100g body wt.). Pretreatment with diethylstilboestrol exerted substantial membrane-destabilizing influence in preputial-gland lysosome samples from orchidectomized rats. Moreover, administration of testosterone to gonadectomized animals resulted in essentially equivalent dose-dependent augmentation of lysosomal enzyme release in preputial-gland preparations of either sex. The membrane stability of lysosome-enriched preparations from uterus, on the other hand, was unaffected by testosterone pretreatment. The sensitivity, specificity and selectivity of the lysosomal response to sex steroids provide evidence for the physiological significance of this phenomenon as a general mechanism for mediation of secondary biochemical transformations in the hormone-stimulated target cell.