Data di Pubblicazione:
2017
Citazione:
Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms / C. Macchi, L. Steffani, R. Oleari, A. Lettieri, L. Valenti, P. Dongiovanni, A. Romero Ruiz, M. Tena Sempere, A. Cariboni, P. Magni, M. Ruscica. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - 454:C(2017), pp. 135-145. [10.1016/j.mce.2017.06.019]
Abstract:
INTRODUCTION:
Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes.
AIM:
To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used.
RESULTS:
Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE-/-, resembling human hemochromatosis.
CONCLUSIONS:
IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Hypogonadism; Iron overload; GnRH; Median eminence; Testes
Elenco autori:
C. Macchi, L. Steffani, R. Oleari, A. Lettieri, L. Valenti, P. Dongiovanni, A. Romero Ruiz, M. Tena Sempere, A. Cariboni, P. Magni, M. Ruscica
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