Enhanced Frequency and Magnitude of Episodic Luteinizing Hormone-Releasing Hormone Discharge as a Hypothalamic Mechanism for Increased Luteinizing Hormone Secretion*

Abstract

LH is secreted by the pituitary in a series of pulses which reflect the episodic release of LRH by the hypothalamus in response to neurally mediated processes. This study examined whether gonadal steroids might exert their negative feedback effects on LH secretion by modulating either the frequency or magnitude of LRH pulses. In the absence of sufficiently sensitive plasma LRH assays, we utilized an indirect method to assess LRH secretion by analyzing the frequency and amplitude of plasma LH pulses and simultaneously measuring the acute pituitary sensitivity to exogenous LRH. Ten normal men received clomiphene citrate to interrupt the LH-estradiol negative feedback loop and thereby stimulate LH secretion. This treatment resulted in an increase (P < 0.05) in the frequency of LH pulses observed on day 8 of the study (4.3 ± 0.26 pulses/6 h) compared to basal (3.2 ± 0.25). The amplitude of spontaneous LH pulses also rose during clomiphene from basal levels of 28 ± 3.2 to a maximum of 58 ± 5.3 ng/ml. pulse on day 8 (P < 0.001). This observed increase did not reflect an enhanced pituitary sensitivity to LRH, since clomiphene markedly blunted the acute response to this releasing factor. The divergence between spontaneous pulse height and acute pituitary sensitivity indicated that increased LRH release must be responsible for the high amplitude LH pulses. Similarly, the rise in pulse frequency probably reflects hypothalamic neural events, since episodic secretion is not intrinsic to the pituitary. (J Clin Endocrinol Metab48: 315, 1979)