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Proliferation and differentiation of the normal endometrium are orderly regulated by female sex steroid hormones. In this connection, development and growth of endometrial cancer have also thought to be controlled in part by sex steroid hormones. Furthermore, some of the sex steroid hormones, progesterone, for example, are used as therapeutic agents in the management of endometrial cancer. The role of estrogen as a promotion factor of endometrial cancer is understood by unopposed estrogen hypothesis, and relative excess of estrogen unopposed by gestagen is regarded as an important factor for the development of endometrial cancer. High dose administration of gestagen has been used as a therapeutic agent of endometrial cancer over these three decades, and now the oral administration of medroxyprogesterone acetate (MPA) is mainstay, with response rate of approximately 30%. However, recently some cases with serious side effect, mainly thrombosis, have been reported. These cases should be regarded as a grave warning to easy usage of MPA. Therefore, the search for more effective and safe way for clinical application have to be requested; for example, clarification of the precise mechanism of anti-tumor effect of MPA on endometrial cancer or development of new hormonal therapeutic agents. Moreover, basic research in the field of cancer and hormone may create a new era in cancer therapy in the future.

Phosphatidylcholine of resting human tonsil lymphocytes contained dipalmitoyl (18 mol%), 1-oleoyl,2-palmitoyl (11 mol%) and dioleoyl (5 mol%) species. 1-Oleoyl and 1-linoleoyl species were also detected in other more highly unsaturated phosphatidylcholine species. The features of phospholipid synthesis in lymphocytes were investigated by incubating cells with radiolabeled precursors. The de novo synthesis of phospholipids occurring in lymphocytes was estimated to be physiologically important, in particular for supplying dipalmitoylglycerophosphocholine and highly unsaturated phosphatidylethanolamine. It was also suggested that diacylglycerol(s) not originating from glycerophosphate is (are) involved in the synthesis of tetraenoic phospholipids. From radioactive palmitic and oleic acids were actively synthesized dipalmitoyl, dioleoyl and 1-oleoyl,2-palmitoyl species of diacylglycerol. The mode of diacylglycerol synthesis was reflected upon phosphatidylcholine formation. The formed polyunsaturated phosphatidylethanolamine was also found to contain 1-oleoyl or 2-palmitoyl species. Radioactive linoleic and arachidonic acids were incorporated predominantly into the C-1 position of diacylglycerol, whereas the majority of the formed phospholipids was of 2-linoleoyl or 2-arachidonoyl species. Labeled stearic acid was exclusively esterified to the C-1 position of the glycerolipids. However, the labeling pattern of molecular species by stearate was considerably deviated from that observed with labeled palmitate. These results indicate that the de novo synthetic pathway operating lymphocytes is primarily responsible for forming 1-unsaturated type of phospholipids. The synthesis of 1-saturated,2-unsaturated species appeared to be due to remodeling of once-formed phospholipids.

Two types of melanosomes were isolated from B16 and Harding Passey (HP) mouse melanomas to elucidate whether there are any features of melanosomal lipids and proteins related to the differences in morphology of melanosomes and in the biological activities of melanoma cells. Biochemical analyses were made to clarify (a) the lipid components of the 2 melanosomes and (b) the lipid and polypeptide compositions of their subfractions, i.e., the outer surface and inner core, resolved by a detergent, Brij-35, separately. We found (a) that the lipid contents in B16 melanosomes were much higher than those in HP, (b) that the B16 and HP melanosomes could be fractionated into a phospholipid-rich outer surface and phospholipid-poor core, (c) that both outer surface and core subfractions of HP were distinct from the corresponding subfractions of B16 with respect to phospholipid contents, (d) that the outer surface of B16 and HP revealed a polypeptide composition similar to each other, although the protein contents of the outer surface were much lower than those of core and (e) that the total melanosomes showed a marked difference in polypeptides between B16 and HP. In addition, both B16 and HP melanosomes revealed the alteration of lipid compositions, e.g., fatty acid acyl chain, similar to that observed during malignant transformation. There was not, however, any significant difference in acyl compositions between B16 and HP. It is likely that melanosomal lipid and protein not only affect the different morphogenesis of melanosomes but also reflect the different biological activities of whole cells, and that lipids, primarily located in the outer surface, regulate the functional aspects of melanosomes.

1. Multiple forms of phosphoinositide-phospholipase C (PLC) were isolated from mastocytoma; two cytosolic forms (cPLC-I, Mr 150,000; cPLC-II, Mr 110,000) and two membrane-associated forms (mPLC-I, Mr 85,000; mPLC-II, Mr 85,000). 2. Four PLC forms differently behaved in substrate specificity and effect of GTP-binding proteins.

1. Mitochondrial and microsomal fractions of rat epididymal adipose tissue incorporated [1-(14)C]acetyl-CoA equally well into various fatty acids by a chain-elongation mechanism. C(18) and C(20) fatty acids were the two major products, and comprised about 80% of the total fatty acids synthesized in both particles. 2. When incubated in air, mitochondria synthesized stearic acid, octadecenoic acid and eicosamonoenoic acid in almost equal amounts (about 20% each), whereas in microsomal fractions, the synthesis of octadecenoic acid was more than fivefold the stearic acid formation. In both fractions, major components of synthesized monoenoic fatty acids were the Delta(11:12) isomers. Hexadecenoic acid and octadecenoic acid from whole adipose tissue contained approx. 11 and 14% of the Delta(11:12) isomer respectively. 3. When mitochondria or microsomal fractions were incubated in nitrogen, there was increased synthesis of stearic acid and palmitic acid and less of C(16) and C(18) monoenoic acids; synthesis of C(20) acids remained predominantly of the monoenoic acids. Determination of the position of the double bond in the monoenoic acids supported the view that the synthesis of hexadecenoic acid and octadecenoic acid involves a desaturase activity, whereas eicosamonoenoic acid and eicosadienoic acid are formed only by elongation of endogenous fatty acids. 4. Most of the radioactivity was found in free fatty acids (63%) and the phospholipid (26%) fraction. In phospholipids, phosphatidylcholine and phosphatidylethanolamine were the two major components. 5. Most of the fatty acids synthesized, including those not normally found in particle lipids (arachidic acid, eicosamonoenoic acid and eicosadienoic acid) were distributed fairly evenly in the phospholipid and free fatty acid fractions. However, stearic acid was found predominantly in the phospholipid fraction.