Androgen regulation of the cellular distribution of the true tissue kallikrein mK1 in the submandibular gland of the mouse

The kallikrein gene family encodes for at least four different proteases in the mouse submandibular gland (SMG): mK1 (true tissue kallikrein), mK9, mK 13, and mK22. These enzymes and many other biologically active proteins are synthesized by the granular convoluted tubule (GCT), a specialized segment of the SMC duct system. The CCT is under multihormonal regulation by andro gens, thyroid hormones, and adrenocortical hormones. Androgens suppress syn thesis of mK1 in the SMG but enhance expression of the other three kallikre ins. We prepared an antibody with limited immunoreactivity for mK1 and used it to examine the effects of androgen status on the distribution of this i sozyme in the SMGs of developing and mature mice by immunoperoxidase staini ng for the light microscope and immunogold labeling for the electron micros cope. In prepubertal mice, every immature GCT cell contains mK1, confined t o an accumulation of small granules in the subluminal cytoplasm. In mature mice, not every GCT cell contains mK1, and in those cells that do there is considerable intergranular variation in the intensity of staining for mK1. GCT cells containing mK1 are much more abundant in the glands of females th an of males, resulting in a peculiar sexually dimorphic mosaic distribution of this isozyme in the mature SMG. Castration of adult males increases the number of GCT cells expressing mK1. Administration of androgen to intact o r castrated males or to intact females reduces the number of cells staining for mK1. In all cases, immunogold labeling for mK1 is confined to secretor y granules. No fine structural differences were noted between cells that we re positively or negatively stained for mK1. Therefore, although GCT cells appear to be composed of a uniform population of cells on the basis of morp hology alone, they are not homogeneous in their content of secretory protei ns. These results indicate that androgen regulation of GCT cells is more co mplex than has been appreciated to date.