An Intractable, Ovary-Independent Impairment in Hypothalamo-Pituitary Function in the Estradiol-Valerate-Induced Polycystic Ovarian Condition in the Rat1

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Abstract
A single injection of estradiol valerate (EV) produces anovulatory acyclicity and polycystic ovaries (PCO) in the rat. Basal serum luteinizing hormone (LH) concentrations are attenuated whereas serum follicle stimulating-hormone (FSH) concentrations are in the high normal range in these animals. Subsequent unilateral ovariectomy restores ovulatory cycles and normal histology in the remaining ovary without correcting the aberrant basal serum gonadotropin concentrations. This suggests that although the blocked surge mechanism is correctable, a second relatively intractable ovary-independent impairment compromises basal gonadotropin production. To identify and characterize this second component, we have examined hypothalamic-pituitary function in PCO rats after bilateral ovariectomy. Adult (200-250 g), normal cyclic Wistar rats were injected with 2 mg EV or with vehicle (control). Nine weeks later all animals were ovariectomized and PCO was confirmed in the EV-heated animals. Animals were killed at 0, 2, 7, 14, and 28 days after ovariectomy, and by hypothalamic content of luteinizing hormone-releasing hormone (LHRH) and pituitary and serum concentrations of LH and FSH were measured. LH and FSH responses to exogenous LHRH were assessed. Serum progesterone, testosterone, and estradiol concentrations were determined at 28 days. Hypothalamic LHRH decreased significantly in all animals over the 28-day period. Although LHRH values did not differ at Time O, by 28 days there was significantly less LHRH in the hypothalami of control than in PCO rats. This pattern of depletion was mirrored by corresponding reciprocal patterns of increasing serum gonadotropin concentrations. However, serum LH concentrations in PCO rats were significantly lower than the gonadotropin concentrations. However, serum LH concentrations in PCO rats were significantly lower than the corresponding concentrations in controls at all post-ovariectomy intervals. Initial pituitary concentrations of LH and FSH were significantly lower in PCO rats (.ltoreq. 50% of control), but by 28 days they were comparable to the elevated control levels. The PCO animals showed an attenuation in LH responses to LHRH and impaired replenishment of pituitary LH following the LHRH stimulation. These parameters were within the control range for FSH. We conclude that there is a permanent impairment in hypothalamo-pituitary function in EV-induced PCO. We suspect that the primary defect is in the hypothalamic LHRH signal and that this defect produces a relatively selective impairment in LH synthesis, storage, and/or release.