Increased melanocyte-lightening activity was found in the plasma of hypophysectomized rats as assayed by direct application to the pituitaries of frogs which had been previously darkened by removal of the hypothalamus. A decrease in this activity by destruction of the hypothalamus of the hypophysectomized rat suggested that MSH release-inhibiting factor (MIF) was involved. Pinealectomy of the hypophysectomized rat or extraction of the plasma with chloroform also decreased the plasma melanocyte-lightening activity, indicating the contribution of melatonin to the lightening effect. The presence of increased amounts of both Pro-Leu-Gly-NH2 (PLG), an MIF, and melatonin in the plasma of hypophysectomized rats, as compared with intact controls, was supported by the use of thin-layer chromatography. In addition, a potentiating action of PLG upon the skin lightening activity of melatonin was observed. These experiments suggest new dimensions to the pineal-hypothalamic-pituitary axis.
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