Delayed puberty and hypogonadism are common complications of chronic renal failure in childhood. In addition to alterations at the gonadal and pituitary level, a reduction of hypothalamic gonadotropin releasing hormone (GnRH) secretion was also observed in castrate uremic rats. The aim of the study was to reveal the uremia-induced changes in the regulation of GnRH release by catecholaminergic neurons. We measured the norepinephrine (NE) concentration in the extracellular fluid of medial preoptic area (MPOA), as well as in the homogenizate of 4 hypothalamic regions (A1 and medial preoptic areas, dorsomedial and periventricular nuclei). Three groups of adult male Sprague-Dawley rats (300 g, n=18 in each) were included. The animals were orchidectomized on day 1 and divided into the following groups: Group-1, sham-operated control rats fed ad libitum; Group-2, sham-operated pair-fed control rats (malnutrition control); Group-3, subtotal (5/6) nephrectomized uremic rats. Guide cannula was implanted into the MPOA of 9 animals of each group on day 12, and a microdialysis probe (CMA/12, Carnegie Medicine) was inserted on day 16. After a 2 h equilibration period, dialysate samples were collected every 10 min for 4 h. In the second part of the study, 9 rats of each group were killed on day 16, fresh frozen slices were cut from the brain, and the 4 nuclei investigated were removed by punching technique. NE concentration was measured by HPLC with electrochemical detection both in the microdialyzate samples (extracellular fluid) and homogenized brain regions(intracellular space). Statistical analysis was performed using the analysis of variance followed by Duncan's test.

Extracellular NE level was significantly (p<0.05) reduced in MPOA of uremic animals (Group-3) compared to that in both control groups. Similarly, we have found a significant (p<0.05) decrease in intracellular NE level in the homogenizate of MPOA of uremic rats compared to that in ad libitum fed control animals (Group-1). However, no significant change in intracellular NE concentration was seen in the other 3 hypothalamic regions examined.

The present experiment provides in vivo evidence for a deficient stimulatory input of superior neuronal systems to the hypothalamic GnRH pulse generator during uremia. According to our data, uremia decreases not only the release, but also the production of NE, a stimulatory neurotransmitter, in the MPOA of rats.