Regulation of Formation and Proposed Structure of the Factor Inhibiting the Release of Melanocyte-Stimulating Hormone

Instituto de Investigación Medica, Mercedes y Martín Ferreyra, Córdoba, Argentina
^†Department of Physiology, The Mount Sinai Medical and Graduate School of the City University of New York, N.Y. 10029
^†The Medical Research Center, Brookhaven National Laboratory, Upton, N.Y.

Abstract

Microsomal preparations from the stalk median eminence of female rats are shown to contain an enzymic activity that is responsible for the formation of MSH-release-inhibiting factor (MSH-R-IF). The amount of this activity remains constant throughout the estrous cycle. The corresponding mitochondrial preparations from the stalk median eminence contain another enzymic principle, estrous cycle-dependent, which competes with the enzyme present in the microsomal preparation for the same “substrate”, and can thereby prevent the formation of MSH-R-IF.

Several neurohypophyseal hormones, analogs, and peptide intermediates have been tested for their intrinsic MSH-R-IF activity and for their ability to be transformed into MSH-R-IF by incubation with microsomal preparations of stalk median eminence from male rats; it is concluded that the enzyme responsible for the formation of MSH-R-IF is an exopeptidase and that the release-inhibiting factor itself is a tripeptide. Oxytocin is converted by the incubation to _L-prolyl-_L-leucylglycinamide; nanogram amounts of this tripeptide inhibit the release of MSH from the pituitary both in vivo and in vitro.