Altered Patterns of Pituitary Secretion and Renal Excretion of Freeα-Subunit during Gonadotropin-Releasing Hormone Agonist-Induced Pituitary Desensitization*

Abstract

Intact LH and free alpha-subunit (FAS) are differentially regulated during GnRH agonist (GnRHa)-induced pituitary desensitization; circulating levels of FAS rise, while LH levels decline. Increased steady state alpha and decreased LH beta mRNA levels in desensitized rat pituitaries suggest that differential regulation occurs at the level of subunit transcription. We assessed a renal contribution to these changes in serum hormone concentrations by studying LH and FAS levels in serum and urine in 15 pubertal children before and during long term GnRHa administration. Before GnRHa, serum LH and FAS were secreted in concordant pulses, and both responded briskly to exogenous GnRH. During GnRHa-induced pituitary desensitization, mean (+/- SEM) serum and urinary LH levels fell [11 +/- 3 vs. 2 +/- 0.2 IU/L (P less than 0.01) and 39 +/- 15 vs. 5 +/- 1 IU/g creatinine (P less than 0.05), respectively), and the LH response to exogenous GnRH was ablated (117 +/- 20 vs. 1 +/- 0.3 IU/L; P less than 0.01). In contrast, despite suppression of FAS pulsatility, mean serum FAS levels rose during GnRHa treatment (204 +/- 23 vs. 405 +/- 50 ng/L; P less than 0.01), and responsiveness to exogenous GnRH was maintained. Paradoxically, urinary FAS levels fell (3.2 +/- 0.9 vs. 1.7 +/- 0.4 micrograms/g creatinine; P less than 0.05) as did its renal clearance (3.1 +/- 0.5 vs. 1.3 +/- 0.1 mL/min.m2; P less than 0.05). We conclude that during GnRHa-induced pituitary desensitization, the gonadotrope maintains the ability to respond to GnRH with FAS release, and the rise in serum FAS is due in part to its diminished renal clearance.