Studies on prolactin. Selective reduction of the disulfide bonds of the ovine hormone

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Abstract
Methods for selective reduction of the disulfide bonds in ovine prolactin are reported. Cleavage of all 3 disulfide bonds abolishes biological activity and denatures the hormone. Reduction-carbamidomethylation of 1 or 2 of the disulfide bridges does not diminish the biological activities in the pigeon crop-sac and mouse mammary gland bioassays. When compared to the native hormone, monomers of these 2 partially reduced-carbamidomethylated derivatives also show only modest changes in properties measured by exclusion chromatography, circular dichroism and immunological cross-reactivities. Cleavage of cystine-4-11 and cystine-191-199, followed by carbamidomethylation, destroys the biological activity of this derivative in a teleost fish bioassay (Gillichthys urinary bladder). Reduction of cystine-4-11 actually increased the teleost potency of this derivative compared to the intact hormone. Since teleost prolactin appears to lack a homolog to the cystine-4-11 disulfide bond in the amino-terminal loop of the ovine hormone, selective reduction of this bond in ovine prolactin may produce a derivative whose properties more closely resemble the fish hormone.