Changes of expression of genes related to the activity of the gonadotrophin-releasing hormone pulse generator in young versus middle-aged male rats.

In females, it is well established that changes in the expression of neurotransmitters and peptides regulating the activity of the gonadotrophin-releasing hormone (GnRH) pulse generator are altered during ageing. By contrast, little is known about whether those age-related changes also occur in males. Therefore, we designed an animal study with orchidectomised young and middle-aged male rats to investigate changes in luteinising hormone (LH) secretion profiles and changes in the mRNA expression of genes regulating the activity of the GnRH pulse generator. Our results demonstrate that middle-aged rats exhibit lower serum LH levels and relatively fewer LH pulses with attenuated amplitude compared to young animals. Furthermore, upon ageing, GnRH mRNA expression is up-regulated in the preoptic area and the septum where GnRH neurones reside. Analysis of mRNA levels of glutamate decarboxylase (GAD) enzymes revealed that GAD(65) and GAD(67) mRNA expression increased in the mediobasal hypothalamus (MBH) and that GAD(67) mRNA levels decreased in the suprachiasmatic nucleus. In addition, we observed an age-related increase of oestrogen receptor (ER)alpha mRNA in the MBH, and both ERalpha and ERbeta mRNA expression was up-regulated in the pituitary of middle-aged rats compared to young animals. Taken together, our data support the existence of a male 'andropause' that is, like the menopause in females, accompanied by changes in neurotransmitter and hormone receptor expression that are involved in regulating the function of the GnRH pulse generator.