Expression and regulation of LRP-2/megalin in epithelial cells lining the efferent ducts and epididymis during postnatal development

Low density lipoprotein receptor-related protein-2/megalin (LRP-2) is a rec eptor belonging to the low density lipoprotein receptor family that mediate s endocytosis and lysosomal degradation of a variety of ligands including a polipoprotein J (Apo J)/clusterin/SGP-2. LRP-2 has been shown to be express ed regionally in the adult rat epididymis. In this study, we describe the p attern of expression of LRP-2 in the efferent ducts and epididymis during p ostnatal development of the rat and examine the role of testicular luminall y derived substances on its expression. The expression of LRP-2 was analyze d immunocytochemically in tissues of normal animals ranging in age from pos tnatal day 7-90 and in 15-day-old efferent-duct-ligated animals sacrificed at later ages, In the efferent ducts, LRP-2 expression, appearing as a dens e band on the epical surface of the nonciliated epithelial cells, was noted as early as day 7, well before the entry of sperm, Sertoli-cell-derived se cretory products, and high levels of androgens. Efferent duct ligation stud ies further revealed that expression under this condition was comparable to controls at all later ages examined, suggesting that the factor regulating its expression was not a luminally derived testicular substance. In normal untreated animals, LRP-2 expression was not apparent at any of the ages ex amined in the proximal initial segment of the epididymis. By comparison, th e distal initial segment, although having no LRP-2 expression from 7-15 day s, showed expression in principal cells by day 21 which intensified at days 29 and 39. However, by day 49 and at later ages (56 and 90), LRP-2 immunor eactivity over principal cells became spotty or with weak or moderate react ivity in some cells and none in others. LRP-2 expression in the intermediat e zone, proximal caput, corpus, and cauda regions also appeared in principa l cells by day 21, intensified at days 29 and 39 and persisted as such at a ll later ages examined, correlating with high levels of androgens shown to occur by day 39. Although LRP-2 expression in the distal caput region was e vident in principal cells at days 21 and 29, it became spotty with weak, mo derate, or absent reactivity over principal cells at all later ages. These data suggest that LRP-2 expression is under the influence of both stimulato ry and region-specific inhibitory factors, Analysis of 15-day-old efferent- duct-ligated animals at all later ages examined revealed that there was no change in LRP-2 expression along the entire epididymis, suggesting that bot h the stimulatory and inhibitory factors are not luminally derived testicul ar substances, The observed pattern of LRP-2 expression in all regions of t he epididymis, except the distal caput region, was similar to that describe d for Apo J internalization by principal cells during postnatal development , showing a correlation between LRP-2 expression and its ligand, Apo J. In summary, LRP-2 expression in the epididymis undergoes region-specific chang es during postnatal development and appears to be influenced by both stimul atory and inhibitory factors, Mel. Reprod, Dev. 53:282-293, 1999, (C) 1999 Wiley-Liss, Inc.