Molecular mechanisms of reappearance of luteinizing hormone receptor expression and function in rat testis after selective Leydig cell destruction by ethylene dimethane sulfonate.

作者: M. Tena-Sempere , A. Rannikko , J. Kero , F.-P. Zhang , I. T. Huhtaniemi

DOI: 10.1210/ENDO.138.8.5325

关键词:

摘要: Considering the major role of LH in control Leydig cell (LC) development and function, we aimed to characterize further pattern receptor (LHR) expression two experimental paradigms: rat treated with ethylene dimethane sulfonate (EDS), which selective destruction preexisting mature LCs induces proliferation differentiation newly formed LCs, a process that takes place presence high levels gonadotropins; EDS-rat dose testosterone (EDS + T), secretion is suppressed, consequently LC after EDS arrested. In rats, serum T was suppressed testicular LHR binding became undetectable on days 5 15 treatment. The messenger RNA (mRNA) profoundly modified: only one splice variants [1.8-kilobase (kb)] persisted, whereas others disappeared. On 20 45 EDS, along repopulation, recovered, mRNA gradually returned resembling controls. similar drop change detected However, 45, no recovery either or longer observed, showing needed induce repopulating at least quantitatively significant level. To gain insight into mechanism(s) by acts precursors, translational status 1.8-kb transcript, persistently expressed analyzed compared 6.8-kb message. polysome distribution analysis total RNA, message highly associated polysomes, variant mainly localized prepolysomal fractions, both testes, thus predicting lower efficiency. addition, considering express LHRs testis, time course reappearance functional receptors mapped evaluating responsiveness human recombinant vitro. No response stimulation EDS. cAMP observed 20, regardless (EDS) T) donor animal. Hence, appearance LHRs, qualitatively, can take absence measurable levels. EDS-treated coincided those pregnenolone, progesterone, T. contrast, LH-induced steroid release indicating steroidogenic developing requires priming. conclusion, low level expression, precursors an LH-independent developmental event, essential for subsequent LH-dependent maturational steps, including onset steroidogenesis increased expression. our results cast doubt truncated (1.8-kb) form mRNA, persists early precursors.

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