CASTRATION INCREASES CELL-DAMAGE INDUCED BY PORPHYRINS IN THE HARDERIAN-GLAND OF MALE SYRIAN-HAMSTER - NECROSIS AND NOT APOPTOSIS MEDIATES THE SUBSEQUENT CELL-DEATH

It is known that the Harderian gland of male Syrian hamster synthesize s a much smaller amount of porphyrins than the gland of the female and that castration greatly increases this synthesis. We have studied in this experimental model the behavior of the different classes of secre tory cells and their role in the synthesis of porphyrins, attempting t o clarify the participation of these compounds in the cell damage lead ing to the formation of clear cells previously described in the gland of females. We have also investigated the mechanism underlying the dea th of these secretory cells after porphyrin accumulation (necrosis vs apoptosis). To achieve this, we have utilized the following techniques : (a) morphometrical; (b) ultrastructural; (c) biochemical (fluorescen ce spectrophotometry); and (d) molecular (DNA nick-end labeling in met hacrylate sections and dot blot analysis). The glands from male hamste rs (serving as control) present a very low rate of damaged cells that progressively rises after castration. This rise runs parallel to that of porphyrin synthesis, porphyrin deposits, and the decrease of Type I I secretory cells. The damage and subsequent death of the secretory ce lls in the gland is produced by the deposit of porphyrins in the mitoc hondrial membrane. This porphyrin accumulation leads to a complete mit ochondrial destruction that finally results in cell death and its secr etion into the lumen. We finally conclude that this event is not a phy siological cell death (apoptosis) but the consequence of the toxic acc umulation of porphyrins (necrosis). (C) 1996 Academic Press, Inc.