Gonadotropin-induced proliferation of endoplasmic reticulum in an androgenic tumor and its relation to elevated plasma testosterone levels.

The development of gonadotropin-induced structural change in a testosterone-secreting Leydig cell tumor and its relationship to plasma testosterone levels were studied in castrate, tumor-bearing mice 2 hr after daily injections of human chorionic gonadotropin (HCG). Tumor cells from control animals were small, averaging less than 1.0 X 10(-9) ml in volume, and were poorly differentiated, having very little smooth endoplasmic reticulum (SER) in their cytoplasm. Average plasma testosterone levels in these mice were near 1.3 ng/ml. Although a five-fold rise in plasma testosterone was measured 2 hr after the first HCG injection, no changes in the endoplasmic reticulum were detected at this time. After the second injection, plasma testosterone rose to only twice control levels, while ultra-areas of mixed rough endoplasmic reticulum and SER. Modest amounts of SER had appeared in many tumor cells after the third injection, and plasma testosterone showed a six-fold rise. Between the third and fourth injections, cell volume increased by about 70% as large accumulations of SER appeared in the cytoplasm of most cells. Plasma testosterone again rose to five times control levels. Increased cell volume and abundant SER were maintained by continuing daily injections of HCG, while the 2-hr plasma testosterone response persisted at five to six times the control level. These findings show that a maximal elevation of plasma testosterone can occur prior to changes in the endoplasmic reticulum of Leydig tumor cells. However, they also suggest that daily repetition of the maximal functional response requires that the cells acquire large quantities of newly produced SER.