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

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-treated animals. Animals were killed at 0, 2, 7, 14, and 28 days after ovariectomy, and 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 0, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Limbic Seizures Alter Reproductive Function in the Female Rat

“…It also changes hypothalamic sensitivity to ovarian steroids (30) and alters the catecholaminergic and adrenergic regulation of the suprachiasmatic nucleus, thought to be the master circadian pacemaker of the hypothalamus (3 1,32). The net result is a seizure-induced andlor E,-induced change in hypothalamic GnRH secretion and LH synthesis, storage andor release (33), leading to perturbations in reproductive cyclicity.…”

“…Human PCOD is characterized by (a) increased basal concentrations of LH and normal or low-normal basal levels of FSH (30), (b) chronic anovulation (39), (c) enlarged ovaries containing follicular cysts at different stages of growth and atresia (40), (d) elevated plasma concentrations of estrone and estradiol, and (e) elevated levels of circulating androgens (41). A number of previous studies attempted to develop the hypothesis that conditions of anovulatory sterility in female rodents may provide models for human PCOD (33,(42)(43)(44)(45). However, although these different rodent models all have polyfollicular ovaries, none exhibit the combination of elevated T, E,, and LH levels that is a common feature of human PCOD.…”

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment

“…Letrozole is a third generation aromatase inhibitor that blocks the conversion of testosterone to estrogen, thus inducing hyperandrogenism. Estradiol valerate is a long-acting estrogen which acts by disturbing hypothalamic gonadotrophin-releasing hormone secretion, which in turns interferes with the secretion and storage of LH (Simard et al 1987).…”

Monosodium Glutamate-lnduced Reductions in Hypothalamic Beta-Endorphin Content Result in Mu-Opioid Receptor Upregulation in the Medial Preoptic Area

“…Anovulatory acyclicity and polycystic ovaries occur in the rat 4-8 weeks following a single subcutaneous injec tion of estradiol valerate (EV) [1][2][3]. Evidence from our laboratory indicates that EV treatment produces an in tractable impairment in the hypothalamic pattern of lu teinizing hormone releasing hormone (LH-RH) delivery [3,4] which, in turn, results in selective defects in pituitary LH production, storage, and release [3].…”

“…Evidence from our laboratory indicates that EV treatment produces an in tractable impairment in the hypothalamic pattern of lu teinizing hormone releasing hormone (LH-RH) delivery [3,4] which, in turn, results in selective defects in pituitary LH production, storage, and release [3]. This cascade of hypothalamic and pituitary defects ultimately translates into a unique attenuated plasma pattern of LH, to which the ovaries respond by becoming polycystic [5][6], Our investigation into the nature of the primary hypo thalamic impairment responsible for this cascade of events has revealed significant alterations in opioid func tion.…”