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 varie ty of steroid-responsive tissues and exhibits a highly regionalized pa ttern of expression in morphologically and functionally distinct segme nts of the mouse epididymis: the highest levels occur in the proximal caput, lower levels occur in the initial segment, and intermediate lev els are found in the distal caput. Castration abolished detectable A-r af expression throughout the epididymis. The administration of exogeno us androgens restored expression to precastrate levels, indicating tha t circulating, rather than intraluminal, levels of androgens are suffi cient to maintain expression. Although overall levels of A-raf were ma intained in androgen-replaced animals, the segment-specific pattern of expression was altered. Elevated levels of A-raf were expressed in th e initial segment relative to those in controls. Coincident with this, the morphology of the epithelial cells in the initial segment of andr ogen-replaced castrates was altered to more closely resemble the morph ology of proximal caput epithelial cells in controls. Similar increase s in A-raf expression and changes in epithelial cell morphology relati ve to those in controls were observed in the initial segments of the c astrate-side epididymis of hemicastrate mice, in epididymis from a ger m 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 req uire germ cells for their production in the testis modulate the androg en-dependent expression of A-raf in the initial segment of the caput e pididymis.