An Increase in Hypothalamic Capacity to Synthesize Prostaglandin E2Precedes the First Preovulatory Surge of Gonadotropins*

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Abstract
Earlier evidence has indicated that prostaglandin (PG) E2 is involved in the physiological mechanism of hypothalamic LHRH release. It is also known that the first preovulatory surge of LH is preceded by an increase in LHRH secretion. The present experiments were performed to determine the ability of the hypothalamus to produce PGE2 before the first gonadotropin surge at puberty. Homogenates of medial basal hypothalami from animals in different phases of puberty were incubated with [14C]arachidonic acid of a high specific activity. The PGs produced were extracted by absorption on octadecylsilyl silica columns, individualized by high pressure liquid chromatography, and detected by measuring the radioactivity in the column effluent. Five PGs were identified: 6-keto-PGF1α, the stable metabolite of prostacyclin (PGI2); thromboxane (TX) B2, the stable metabolite of TXA2; PGF2α; PGE2; and PGD2. At all phases of puberty, PGD2 was the predominant PG produced from arachidonic acid. The relative amounts of PGs produced were PGD2 > 6-keto PGF1α > PGF2α = PGE2 > TXB2. Only the synthesis of PGE2 underwent changes in relation to the reproductive condition of the animal. PGE2 synthesis increased significantly between the anestrous and 1300 h of the late (first) proestrous phases of puberty. At this latter time, the first preovulatory LH surge had started, with LH levels increasing to about 25% of peak values, which were reached at 1600 h. PGE2 synthesis decreased on the day of first estrus. The increase in hypothalamic PGE2 synthesis correlated with the pubertal increase in ovarian estrogen secretion, as measured by the changes in uterine weight that encompass the day of the first LH surge. Administration of estradiol benzoate to anestrous rats, to evoke a premature LH surge, enhanced hypothalamic synthesis of PGE2 without affecting the production of the other PGs, thus mimicking the changes observed during normal puberty. The results indicate that the capacity of the hypothalamus to synthesize PGE2 increases during the hours preceding the first preovulatory surge of gonadotropins and that such an activation is, to a significant extent, dependent on an elevation in circulating estrogen levels. It is suggested that this change in PGE2 synthesis represents an important component of the maturational process by which the hypothalamus acquires the capability of releasing a preovulatory surge of LHRH.