The segment-specific pattern of A-raf expression in the mouse epididymis is regulated by testicular factors

The protooncogene homolog A-raf is expressed at high levels in a variety of steroid-responsive tissues and exhibits a highly regionalized pattern of expression in morphologically and functionally distinct segments of the mouse epididymis: the highest levels occur in the proximal caput, lower levels occur in the initial segment, and intermediate levels are found in the distal caput. Castration abolished detectable A-raf expression throughout the epididymis. The administration of exogenous androgens restored expression to precastrate levels, indicating that circulating, rather than intraluminal, levels of androgens are sufficient to maintain expression. Although overall levels of A-raf were maintained in androgen-replaced animals, the segment-specific pattern of expression was altered. Elevated levels of A-raf were expressed in the initial segment relative to those in controls. Coincident with this, the morphology of the epithelial cells in the initial segment of androgen-replaced castrates was altered to more closely resemble the morphology of proximal caput epithelial cells in controls. Similar increases in A-raf expression and changes in epithelial cell morphology relative to those in controls were observed in the initial segments of the castrate-side epididymis of hemicastrate mice, in epididymis from a germ cell-deficient strain of mutant mice, and in epididymis from intact mice supplemented with exogenous testosterone. These studies indicated that testicular products, such as spermatozoa, or substances that require germ cells for their production in the testis modulate the androgen-dependent expression of A-raf in the initial segment of the caput epididymis.