Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo

Abstract

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)‐induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS‐treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad‐ADM, an adeno‐associated virus vector that expressed ADM. Then, rat testes were collected for 3β‐hydroxysteroid dehydrogenase (3β‐HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor‐1 (SF‐1), liver receptor homologue‐1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3β‐HSD, cytochrome P450 17α‐hydroxylase/17, 20 lyase (CYP17) and 17β‐hydroxysteroid dehydrogenase (17β‐HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF‐1, LRH1, Nur77, StAR, P450scc, 3β‐HSD, CYP17 and 17β‐HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.