Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) - a novel theory for the development of late onset hypogonadism in obese men

Basic and Clinical Andrology

Commentary

Kelton Tremellen¹ 

[1] Department of Obstetrics, Gynaecology and Reproductive Medicine, Flinders University, Adelaide, South Australia, Australia;

关键词: Male hypogonadism;    Testosterone;    Endotoxin;    Lipopolysaccharide (LPS);    Intestinal microbiome;    Hypogonadisme masculin;    Testostérone;    Endotoxine;    Lipopolysaccharide (LPS);    Microbiome intestinal;   

DOI  :  10.1186/s12610-016-0034-7

 received in 2016-03-17, accepted in 2016-05-24,  发布年份 2016

来源: Springer

【 摘 要 】

Obesity is an increasing public health problem, with two-thirds of the adult population in many Western countries now being either overweight or obese. Male obesity is associated with late onset hypogonadism, a condition characterised by decreased serum testosterone, sperm quality plus diminished fertility and quality of life. In this paper we propose a novel theory underlying the development of obesity related hypogonadism- the GELDING theory (Gut Endotoxin Leading to a Decline IN Gonadal function).Several observational studies have previously reported an association between obesity related hypogonadism (low testosterone) and systemic inflammation. However, for the first time we postulate that the trans-mucosal passage of bacterial lipopolysaccharide (LPS) from the gut lumen into the circulation is a key inflammatory trigger underlying male hypogonadism. Obesity and a high fat/high calorie diet are both reported to result in changes to gut bacteria and intestinal wall permeability, leading to the passage of bacterial endotoxin (lipopolysaccharide- LPS) from within the gut lumen into the circulation (metabolic endotoxaemia), where it initiates systemic inflammation. Endotoxin is known to reduce testosterone production by the testis, both by direct inhibition of Leydig cell steroidogenic pathways and indirectly by reducing pituitary LH drive, thereby also leading to a decline in sperm production.In this paper we also highlight the novel evolutionary benefits of the GELDING theory. Testosterone is known to be a powerful immune-suppressive, decreasing a man’s ability to fight infection. Therefore we postulate that the male reproductive axis has evolved the capacity to lower testosterone production during times of infection and resulting endotoxin exposure, decreasing the immunosuppressive influence of testosterone, in turn enhancing the ability to fight infection. While this response is adaptive in times of sepsis, it becomes maladaptive in the setting of “non-infectious” obesity related metabolic endotoxaemia.

【 授权许可】

CC BY   
© The Author(s). 2016