The apparent paradox of the negative and positive feedback control system on gonadotropin secretion.

The separate and interactive effects of estradiol (E2) and luteinizing hormone-releasing factor (LRF) on the dynamics of LH storage and release were studied. Measurements were made of the serum gonadotropin responses to submaximal doses of LRF, given as brief pulses or infused over an extended period to normal women at various stages of the follicular phase of their menstrual cycles and to hypogonadal women with and without estrogen treatment. The two-pool concept of pituitary gonadotropin was verified; the dynamic responses of the two pools to the inputs of LRF and E2 were investigated and related to pituitary properties of sensitivity and reserve. Our results indicate that LRF appears to serve as a primary drive on the gonadotrophs, stimulating gonadotropin synthesis and storage (second pool), as well as release (first). E2 for the most part, amplifies the action of LRF except that it impedes LRF-induced release of gonadotropin. E2 augments the second pool activity (reserve) preferentially, and the relative activity of the first pool appears to be influenced by the E2-dependent self-priming effect of LRF. The interactions of the various elements of the system, when combined, provide a U-shaped curve to describe the over-all capacity of the gonadotrophs as a function of a broad range of E2 inputs. Negative and possitive feedback of E2 are revealed to operate by different mechanisms and to represent different segments of a single U-shaped curve rather than paradoxically disparate actions.