The rapid effects of luteinizing hormone releasing hormone agonists and antagonists on the mouse pituitary in vitro.
The effect of luteinizing hormone releasing hormone (LHRH) and its analogs on the release of FSH and LH by 20 day old whole mouse pituitary incubated in vitro for 3-4 hrs was investigated. Three agonistic analogs (AY 25650, 25205 and Buserelin) all of which are reported to be superactive in vivo showed approximately the same potency in this in vitro test system. Preincubation of the pituitaries for 1 h with the antagonistic analogs [Ac Dp Cl Phe1,2, D Trp3, D Phe6, D Ala10] LHRH and [Ac Dp Cl Phe1,2, D Trp3, D Arg6, D Ala10] LHRH inhibited the secretion of LH and FSH induced by 2.5 x 10(-9)M LHRH. The inhibitory response was dose dependent. The continued presence of the antagonists was not required for effective suppression of the LHRH effect. Experiments designed to find out the minimum time required for eliciting suppression of LHRH revealed that preincubation of the pituitary with the second antagonist for 5 mins followed by removal was adequate to produce effective inhibition of gonadotropin release. At lower doses of the antagonist, LH release was more effectively inhibited than FSH release. The results suggest that antagonistic analogs can effectively bind to LHRH receptors in the whole pituitary incubation preventing the subsequent action of LHRH. With the present incubation system assessment of bioactive LH and FSH release is possible within 24 hrs.
D000595:Amino Acid Sequence; D000818:Animals; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship
D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone