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Methotrexate (MTX) was first conjugated to antibovine serum albumin IgG (antiBSA) or its F(ab)2 fragment to define conditions for retention of drug and antibody activity. With identical drug: protein molar ratios, incorporation in the F(ab)2 fragment was lower than in intact antiBSA, an observation consistent with analysis of the number of lysine residues (22 in F(ab)2 compared to 40 in antiBSA). In either case, up to approximately 10 mol MTX could be incorporated per mol protein, with recovery of 70% of the protein. At an incorporation ratio of 6 mol MTX per mol protein, MTX-antiBSA retained 100% of antibody activity and MTX-F(ab)2-antiBSA retained 75%. MTX-antiBSA and MTX-F(ab)2antiBSA were equally potent in vitro inhibitors of dihydrofolate reductase. Conjugates prepared from antiEL4 IgG (AELG) and from F(ab)2AELG significantly increased survival in EL4 lymphoma-bearing mice compared with mice receiving equal amounts (5 mg MTX/kg) of free MTX, MTX linked to the F(ab)2 fragment of normal rabbit IgG, or a simple mixture of MTX and F(ab)2AELG. MTX-AELG at this dose level produced longer survival than MTX-F(ab)2AELG (0.005 less than P less than 0.01).

SUMMARY Ovariectomy on day 17 of pregnancy in rats that normally give birth on day 23 induced lactogenesis and foetal resorption but did not alter the pattern of change in pituitary or plasma prolactin concentration. Plasma prolactin levels increased significantly in both ovariectomized and sham-operated animals from days 18–22 of pregnancy. This suggests that factors other than ovarian products control the rise in late pregnancy of plasma prolactin in the rat. The results support earlier reports that progesterone withdrawal may be the lactogenic trigger in the rat.

SUMMARY Perphenazine given on day 18 of pregnancy and each day following caused large increases in plasma prolactin levels in rats as measured on days 19–23. Pituitary prolactin was depleted on day 19, but subsequently returned to slightly above control values. Adrenal weight was significantly increased by perphenazine treatment suggesting increased production of adrenocorticotrophin and glucocorticoids. The increased prolactin levels caused no significant change on any day in either mammary lactose, glucose, RNA or DNA concentrations or the RNA:DNA ratio. The findings support earlier reports that an increased level of plasma prolactin during pregnancy does not by itself induce lactogenesis in the rat.

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