title: Biosynthesis of ecdysteroid hormones by crustacean Y-organs: conversion of cholesterol to 7-dehydrocholesterol is suppressed by a steroid 5 alpha-reductase inhibitor.
abstract: A pair of glands (Y-organs) in crustaceans synthesize and secrete ecdysteroid hormones; the obligate precursor for synthesis is circulating cholesterol. Ecdysteroid output by the Y-organs is regulated negatively by an eyestalk neurosecretory peptide, molt-inhibiting hormone (MIH). The question was addressed, does MIH suppress ecdysteroid synthesis by decreasing cholesterol supply (uptake) or its utilization or both? Experiments were conducted with Y-organs in vitro from the crab, Menippe mercenaria, in the presence of labeled cholesterol, with or without the steroid 5 alpha-reductase inhibitor, L-645390 (Merck). Other experiments superimposed the presence or absence of eyestalk extract containing MIH activity. L-645390 greatly depressed incorporation of cholesterol into an early intermediate, 7-dehydrocholesterol and into secreted ecdysteroids. At the same time, cholesterol accumulated in the Y-organs, to levels significantly higher than in untreated controls. MIH alone depressed both cholesterol uptake and incorporation. MIH together with L-645390 produced the greatest depression of cholesterol incorporation while also preventing the cholesterol accumulation seen with L-645390 alone. These results indicate that cholesterol uptake and its metabolic utilization in Y-organs are separable events representing separate sites of regulation by MIH.
authors.affiliation: Department of Biological Sciences, University of Iowa, Iowa City 52242.
authors.forename: E
authors.initials: E
authors.lastname: Spaziani
authors.forename: W L
authors.initials: WL
authors.lastname: Wang
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D003386:Brachyura / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D003684:Dehydrocholesterols / Q000378:metabolism*; D003864:Depression, Chemical; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D026461:Ecdysteroids; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007447:Invertebrate Hormones / Q000096:biosynthesis* / Q000494:pharmacology*; D008297:Male; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D003684:Dehydrocholesterols; D026461:Ecdysteroids; D007447:Invertebrate Hormones; D013256:Steroids; C012445:molt-inhibiting hormone; D013196:Dihydrotestosterone; C047523:17-N,N-diisopropylcarbamoyl-4-azaandrostan-3-one; D002784:Cholesterol; C016705:7-dehydrocholesterol