Histidine decarboxylase inhibitors: a novel therapeutic option for the treatment of leydigioma.

Recent reports indicate an increase in Leydig cell tumor (LCT) incidence. Radical orchiectomy is the standard therapy in children and adults, although it entails physical and psychosocial side effects. Testis-sparing surgery can be a consideration for benign LCT of 2.

Heme oxygenase-1 arrests Leydig cells functions and impairs their regulation by histamine.

Testicular Leydig cells (LC) are modulated by several pathways, one of them being the histaminergic system. Heme oxygenase-1 (HO-1), whose upregulation comprises the primary response to oxidative noxae, has a central homeostatic role and might dysregulate LC functions when induced. In this report, we aimed to determine how hemin, an HO-1 inducer, affects LC proliferative capacity and whether HO-1 effects on LC functions are reversible.

Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys.

Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular interstitium, with recent increased incidence. Symptoms include precocious puberty in children; and erectile dysfunction, infertility and/or gynaecomastia, in adults. So far, scientific evidence points to aromatase (CYP19) overexpression and excessive oestrogen and insulin-like growth factor (IGF) -1 production as responsible for Leydig-cell tumourigenesis.

H4 histamine receptors inhibit steroidogenesis and proliferation in Leydig cells.

The histamine H4 receptor (HRH4), discovered only 13 years ago, is considered a promising drug target for allergy, inflammation, autoimmune disorders and cancer, as reflected by a steadily growing number of scientific publications and patent applications. Although the presence of HRH4 has been evidenced in the testis, its specific localization or its role has not been established. Herein, we sought to identify the possible involvement of HRH4 in the regulation of Leydig cell function.

Proliferative effect of histamine on MA-10 Leydig tumor cells mediated through HRH2 activation, transient elevation in cAMP production, and increased extracellular signal-regulated kinase phosphorylation levels.

Mast cells (MC) occur normally in the testis with a species-specific distribution, yet their precise role remains unclear. Testicular MC express histidine decarboxylase (HDC), the unique enzyme responsible for histamine (HA) generation. Evidence to date supports a role for HA as a local regulator of steroidogenesis via functional H₁ and H₂ receptor subtypes (HRH1 and HRH2, respectively) present in Leydig cells.

Galectin-1: biphasic growth regulation of Leydig tumor cells.

Galectin-1 (Gal-1) is a widely expressed beta-galactoside-binding protein that exerts pleiotropic biological functions. To gain insight into the potential role of Gal-1 as a novel modulator of Leydig cells, we investigated its effect on the growth and death of MA-10 tumor Leydig cells. In this study, we identified cytoplasmic Gal-1 expression in these tumor cells by cytofluorometry.

Characterization of L-arginine transport in adrenal cells: effect of ACTH.

Nitric oxide synthesis depends on the availability of its precursor L-arginine, which could be regulated by the presence of a specific uptake system. In the present report, the characterization of the L-arginine transport system in mouse adrenal Y1 cells was performed. L-arginine transport was mediated by the cationic/neutral amino acid transport system y+L and the cationic amino acid transporter (CAT) y+ in Y1 cells.