Episodic Secretion of Luteinizing Hormone-Releasing Factor (LRF) in the Human1

To determine the relationship between hypothalamic secretion of LRF and pituitary secretion of LH, LRF activity was estimated by a semi-quantitative bioassay and human LH was measured by radioimmunoassay in samples drawn every 5–10 inin over a 70- to 90-min period from the peripheral blood of 5 human subjects with a variety of states of gonadal function. The LRF activity bioassay was based on changes in plasma radioimmnoassayable LH in ovariectomized, estrogen and progesterone-treated rats after intravenous injection of test substance. The assay is sensitive enough to detect LRF activity in as little as 1 ml of plasma. LH levels showed episodic fluctuations in a normal male, 2 testosterone-deficient men, an estrogen-treated, castrated man, and a normal woman studied in pre and postovulatory periods. Episodic fluctuations in plasma LRF activity also occurred in samples from all subjects. Estimated from a bioassay standard curve of responses to synthetic LRH 15 samples from a normal man contained LRF activity equivalent to 10–50 pg LRH/ml. Most samples from other subjects contained equivalent amounts of LRF activity but 4 of 25 samples from testosterone-deficient men contained LRF activity equivalent to 200–300 pg LRH/ml and 5 of 15 samples from a castrated, premarin-treated man contained LRF activity equivalent to 80–120 pg LRH/ml. From the woman, 4 of 30 follicular samples, 12 of 30 midcycle samples and 5 of 45 luteal phase samples contained LRF activity equivalent to 50–400 pg LRH/ml, indicating episodic LRF activity release throughout the cycle and increased LRF activity release during the midcycle. Rapid fluctuations in LRF activity are interpreted as evidence for episodic secretion of hypothalamic LRH. While increased numbers of LRF activity spikes were associated with higher mean LH levels, episodic fluctuations in LRF activity were not correlated with subsequent episodic fluctuations in LH.