Differential Control of Luteinizing Hormone and Follicle-Stimulating Hormone Secretion by Luteinizing Hormone-Releasing Hormone Pulse Frequency in Man*

To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low 28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively, and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response.