IMMUNOREACTIVE AND BIOACTIVE LUTEINIZING-HORMONE IN PUBERTAL PATIENTSWITH 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 secre tion from plasma concentration measurements is confounded by alteratio ns in hormone metabolic clearance. To simultaneously investigate LH se cretion and clearance in children, we performed multiple-parameter dec onvolution analysis of 11-hour over night serum LH concentration-time series of bioactive (bio-LH) and immunoreactive (i-LH) hormone in 36 p ubertal 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 treat ed by dialysis, and 12 were studied after successful renal transplanta tion. 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 conserva tive treatment or after renal transplantation was inversely correlated with glomerular filtration rate (GFR) (r = -0.70; P < 0.0001). (2) Pu lsatile 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 conserv ative treatment or after transplantation, a significant positive corre lation 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 attrib utable to a halving of the LH mass secreted per burst in patients on c onservative (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 freque ncy was not different between controls and treatment groups. (4) The r elative contribution of apparent basal LH release to total secretion r ates 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, bu t 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 signific ant 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 (conservati ve treatment). In the transplant patients, none of the secretory and c learance characteristics was significantly different from controls. In conclusion, the secretory pattern of LH in uremic pubertal children i s characterized by a distinct increase in plasma half-life, and a redu ction of the LH secretion rate compatible with deficient GnRH signal s trength and/or pituitary responsiveness. Possibly due to accumulation of as yet undefined immunoreactive but biologically inactive LH fragme nts, apparent basal secretion of i-LH but not bio-LH is relatively inc reased in dialyzed patients, resulting in a disproportionate increase of i-LH compared to bio-LH mean plasma concentrations.