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

Abstract:

: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. It was also evaluated if HO-1 interacts in any way with histamine, affecting its regulatory action over LC. MA-10 and R2C cell lines and immature rat LC were used as models. Firstly, we show that after a 24-h incubation with 25 µmol/L hemin, LC proliferation is reversibly impaired by cell cycle arrest in G2/M phase, with no evidence of apoptosis induction. Even though steroid production is abrogated after a 48-h exposure to 25 µmol/L hemin, steroidogenesis can be restored to control levels in a time-dependent manner if the inducer is removed from the medium. Regarding HO-1 and histamine interaction, it is shown that hemin abrogates histamine biphasic effect on steroidogenesis and proliferation. Working with histamine receptors agonists, we elucidated that HO-1 induction affects the regulation mediated by receptor types 1, 2 and 4. In summary, HO-1 induction arrests LC functions, inhibiting steroid production and cell cycle progression. Despite their reversibility, HO-1 actions might negatively influence critical phases of LC development and differentiation affecting their function as well as other androgen-dependent organs. What's more, we have described a hitherto unknown interaction between HO-1 induction and histamine effects.

journal_name

J Mol Endocrinol

authors

Raices T,Varela ML,Monzón CM,Correa Torrado MF,Pagotto RM,Besio Moreno M,Mondillo C,Pignataro OP,Pereyra EN

doi

10.1530/JME-19-0063

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

187-197

issue

3

eissn

0952-5041

issn

1479-6813

pii

JME-19-0063.R2

journal_volume

63

pub_type

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