Activation of luteinizing hormone release from pituitary cells by polycations.
In the present work we examined the effect of cationic polymers on the pituitary gonadotrope. Such polymers are widely used to anchor gonadotropes and other cell types to culture dishes and other substrata to which they are not normally adherent. Homopolymers of Lys (eight size classes from 4,000-700,000 daltons) stimulate Ca+2-dependent LH release from pituitary cell cultures. In contrast, release does not occur in response to the epsilon-CBZ or succinyl derivatives (which have no internal charge) or in response to polymers of L-Glu, D-Glu, or Gly. The observation that polymers of D-Lys, L-Lys, and L-Arg all stimulate LH release with similar efficacy and potency indicates that simple charge interactions, rather than interaction with specific polymer-binding sites, are the cause of LH release. Since monomeric Lys neither stimulates LH release nor competitively inhibits release in response to Lys polymers, it appears that multiple charge coordination by Lys polymers is responsible for activation of the release mechanism. Putrescine, spermine, and spermidine (which have more closely spaced charges) do not stimulate LH release, suggesting that a certain minimal distance of charge separation must occur to obtain efficacy. The reduced potency of heteropolymers of Lys (spaced with Ala or Tyr) suggests that a maximal effective distance also exists. Consecutive and concomitant incubation studies indicate that LH released in response to poly-L-Lys or GnRH comes from the same pool as that released by GnRH. The time courses of release are similar for the two compounds.
D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011107:Polylysine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D013329:Structure-Activity Relationship
D002412:Cations; D010455:Peptides; D011107:Polylysine; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone