The Regulation of Luteinizing Hormone Secretion by Estrogen: Relationships among Negative Feedback, Surge Potential, and Male Stimulation in Juvenile, Peripubertal, and Adult Female Mice*

These experiments queried the potential for developmental change in the positive and negative feedback sensitivities of LH secretion to estradiol. Serum LH levels were compared in juvenile, peripubertal, and adult female mice after ovariectomy and challenge with a variety of 4-day steroid treatments. Since male stimuli accelerate the attainment of puberty in this species, comparisons also were made between age- and weight-matched groups of pre- vs. postpubertal females, obtained by housing them in either the presence or absence of males. The following conclusions were derived from eight experiments. 1) Progressively more estradiol is required to suppress the postovariectomy rise in serum LH as the female mouse develops the juvenile stage to full adulthood. 2) This slow, progressive change is due in part to a steadily increasing capacity to secrete LH when unhindered by any negative feedback regulation by the ovary; it is not due to developmental changes in estradiol metabolism. 3) The LH surging mechanism is functional and already coupled to its circadian oscillator in the juvenile mouse, but surges of adult magnitude could not be induced with exogenous steroid until the peripubertal period. 4) The estradiol requirements for preovulatory LH surging change markedly after the peripubertal stage of development; a wide range of temporal changes in blood estradiol levels will elicit LH surging in the adult mouse, but the immature female requires a rigid pattern of change involving only a narrow range of blood levels of this steroid. 5) Exposure of peripubertal females to male stimuli alters neither their negative feedback sensitivity to estradiol nor their estrogen requirements for LH surging. These conclusions are integrated into two working models that focus first on the estrogen requirements for LH surging in the adult mouse, and second on the maturation of this process and the attainment of pubertal ovulation. (Endocrinology 108: 506, 1981)