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Peptidyl Proline Hydroxylase in Adult, Developing, and Neoplastic Rat Tissues¹

Department of Biological Chemistry, Harvard Medical School, and Cancer Research Institute, New England Deaconess Hospital, Boston, Massachusetts 02215

A sensitive assay system, optimally supplemented with tritiated protocollagen substrate and cofactors, is described which is suitable for determining the peptidyl proline hydroxylase (PPH) content of a wide spectrum of rat tissues. In most tissues, less than 50% of the total activity was soluble; the particulate portion of the activity (concentrated in the mitochondrial and microsomal fractions) was doubled by pretreatment with Triton X-100.

Among normal adult tissues, lung had the highest total PPH activity (2.4 times that of liver) and small intestine had the lowest (25% that of liver). In brain and lactating mammary gland, the activity was similar to that in skin (60% of that in liver). Fetal tissues contained 3 to 8 times more PPH than the corresponding adult tissues, and a much lower portion of the total activity was soluble.

In four tissues studied in detail (lung, liver, kidney, and brain), the total PPH declined rapidly during the last few days of gestation; brain attained its low adult value before term, whereas the other three tissues continued to decrease in the course of postnatal development. An injection of cortisol to fetal rats enhanced the decline of PPH in lung, liver, and skull. These experiments suggest that during normal differentiation the decline in collagen synthesis is initiated by fetal glucocorticoid secretion which is maximal on the 19th gestational day.

PPH activity appears to be a sensitive indicator of neoplastic growth. In renal, mammary, muscle, and hepatic tumors, the PPH activities were 4 to 10 times higher than in the cognate adult tissue. Even in well-differentiated, slow-growing tumors, the activity was considerably higher than in any normal, mature, or immature tissue, with the exception of the skull and lung of the 19-day-old fetus.

¹ This investigation was supported by USPHS Grant CA 08676 from the National Cancer Institute, Grants AM 00567 and AM-K6-2018 from the National Institute of Arthritis, Metabolism and Digestive Diseases, and by United States Atomic Energy Commission Contract AT (11-1)-3085 with the New England Deaconess Hospital.

Received 10/11/74. Accepted 12/30/74.