IMMUNOREACTIVE AND BIOACTIVE LUTEINIZING-HORMONE IN PUBERTAL PATIENTS WITH CHRONIC-RENAL-FAILURE

Disturbed pulsatile LH secretion has been suggested to play a role in the etiology of delayed puberty and disturbed reproductive function in chronic renal failure (CRF), but interpretation of gonadotropin secretion from plasma concentration measurements is confounded by alterations in hormone metabolic clearance. To simultaneously investigate LH secretion and clearance in children, we performed multiple-parameter deconvolution analysis of 11-hour over night serum LH concentration-time series of bioactive (bio-LH) and immunoreactive (i-LH) hormone in 36 pubertal patients (18 boys) with various degrees of CRF and 10 healthy controls matched for sex and pubertal stage. Twelve patients received conservative treatment for advanced but compensated CRF, 12 were treated by dialysis, and 12 were studied after successful renal transplantation. We observed that: (1) the mean (+/- SE) plasma half-lives of bio-LH and i-LH were increased in the dialysis group (155 +/- 47 and 201 +/- 31 min) and in the patients on conservative treatment (148 +/- 45 and 135 +/- 70 min) compared to controls (59 +/- 28 and 63 +/- 21 min; all P < 0.05). The plasma half-life of bio-LH in patients on conservative treatment or after renal transplantation was inversely correlated with glomerular filtration rate (GFR) (r = -0.70; P < 0.0001). (2) Pulsatile bio-LH production rate was independently affected by pubertal stage (P = 0.018) and treatment status (P = 0.017), increasing across pubertal stages and being significantly lower in dialysis patients (20 +/- 4 IU/liter * 11 hr) and patients on conservative treatment (28 +/- 9) than in controls (43 +/- 9; all P < 0.05). In patients on conservative treatment or after transplantation, a significant positive correlation between pulsatile bio-LH production rate was observed (r = 0.53; P < 0.008). Pulsatile i-LH secretion rate was significantly reduced only in dialysis patients (15 +/- 34 vs. 46 +/- 18; P < 0.05). (3) The reduction of pulsatile i-LH and/or bio-LH production rates was attributable to a halving of the LH mass secreted per burst in patients on conservative (bio-LH: 4.9 +/- 1.9 IU/liter) and dialysis treatment (bio-LH: 3.2 +/- 0.7, i-LH: 2.4 +/- 0.6 IU/liter) versus controls (bio-LH: 6.9 +/- 1.3, i-LH: 5.4 +/- 2.1 IU/liter), whereas the LH pulse frequency was not different between controls and treatment groups. (4) The relative contribution of apparent basal LH release to total secretion rates was higher (25 +/- 11%) in patients on dialysis than in controls (6.8 +/- 3.9%; P < 0.0.05). (5) Mean plasma concentrations of i-LH, but not bio-LH, were significantly elevated in the uremic children. The reduction of mean bio-LH/i-LH ratio in the uremic children was due to the relative increase in basal i-LH secretion, resulting in a significant reduction of the bio-LH/i-LH ratio of total LH secretion rates in patients on conservative treatment (1.14 +/- 0.2 vs. 2.2 +/- 0.2) and dialysis (1.5 +/- 0.24), whereas the bio-LH/i-LH ratio of plasma half-lives was similar (dialysis) to controls or even increased (conservative treatment). In the transplant patients, none of the secretory and clearance characteristics was significantly different from controls. In conclusion, the secretory pattern of LH in uremic pubertal children is characterized by a distinct increase in plasma half-life, and a reduction of the LH secretion rate compatible with deficient GnRH signal strength and/or pituitary responsiveness. Possibly due to accumulation of as yet undefined immunoreactive but biologically inactive LH fragments, apparent basal secretion of i-LH but not bio-LH is relatively increased in dialyzed patients, resulting in a disproportionate increase of i-LH compared to bio-LH mean plasma concentrations.