Defective Central Nervous System Dopaminergic Function in Rats with Estrogen-Induced Pituitary Tumors, as Assessed by Plasma Prolactin Concentrations*

Casanueva, Felipe F.; Locatelli, Vittorio; Flauto, C.; Zambotti, F.; Ge, Bao-Feng; Rossi, G. L.; Müller, E. E.

doi:10.1210/endo-110-2-590

Cited by 70 publications

(38 citation statements)

References 30 publications

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“…The present studies confirm that estradiol induces a prolonged elevation in serum prolactin concentrations which is accompanied by a selective and progressive decrease in DA concentrations in the median eminence. These findings are in agreement with previously published reports [3,13,14,28]. The relationship between the estradiol-induced decrease in the concentra tions of DA in the median eminence and TIDA neuronal activity and function is not clear.…”

Section: Discussionsupporting

confidence: 90%

“…The neurochemical mechanisms by which long-term estrogen treatment cause these altera tions are unclear. The changes may represent a decrease in the number of TIDA neurons, since long-term estradiol has been suggested to cause cytopathological changes in the arcuate nucleus [2,3]. On the other hand, the estrogen-in duced changes may be related to a decrease in the activity and function ofTIDA neurons resulting from a subsensitivi ty to the stimulatory actions of prolactin.…”

mentioning

confidence: 99%

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Long-Term Treatment with Estradiol Induces Reversible Alterations in Tuberoinfundibular Dopaminergic Neurons: a Decreased Responsiveness to Prolactin

Demarest

Riegle²,

Moore

1984

Neuroendocrinology

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Previous studies have demonstrated that short-term (3–5 days) treatment with estradiol increases the rate of turnover and synthesis of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence by virtue of the ability of this hormone to increase circulating concentrations of prolactin. The present studies were undertaken to examine the long-term effects of estradiol on serum prolactin concentrations and TIDA neuronal activity (estimated by the rate of DOPA accumulation in the median eminence after the administration of a decarboxylase inhibitor). Female rats, ovariectomized for 2 weeks, were implanted subcutaneously with silastic capsules containing estradiol benzoate and sacrificed 6,12 and 18 days after capsule implantation. Serum prolactin concentrations were markedly increased at 6,12 and 18 days whereas the rate of DOPA accumulation was increased at 6 days but not at 12 days, and was decreased at 18 days. The concentration of DA in the median eminence was reduced at 6 days and further reduced at 12 and 18 days. The low rate of DOPA accumulation in the median eminence despite the high circulating concentrations of prolactin suggests that long-term estradiol treatment reduces the ability of TIDA neurons to respond to prolactin. This was confirmed by the finding that direct intracerebroventricular (icv) injections of prolactin increased the rate of DOPA accumulation in the median eminence of sham-implanted rats but not in 18 day estradiol-treated rats. To determine if the effects of estradiol were reversible, ovariectomized rats were implanted with estradiol-containing capsules for 18 days. The capsules were then removed and the animals sacrificed at various times up to 18 days later. The elevated serum concentrations of prolactin returned to control values within 18 days after removing the capsules, and the reduced DA concentrations in the median eminence increased but were still less than control after 18 days. On the other hand, the rate of DOPA accumulation in the median eminence increased progressively after removing the capsules reaching values greater than control by 18 days. These results suggest that there may be a rebound increase in the sensitivity of TIDA neurons to prolactin in rats that had the estradiol capsules removed. This was substantiated by the fact that icv prolactin caused a greater increase in the rate of DOPA accumulation in the postestradiol group of rats. These results suggest that long-term estradiol treatment reduces the activity of TI DA neurons, in part by attenuating their responsiveness to prolactin, and that termination of estradiol treatment results in a rebound increase in the sensitivity of TIDA neurons to prolactin. The decreased responsiveness of TIDA neurons induced by estradiol does not appear to be a consequence of elevated levels of circulating prolactin induced by this treatment, since chronic treatment with haloperidol for either 11 or 22 days induced similar elevations of circulating prolactin with an associated increase in the rate of DOP...

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Long-Term Treatment with Estradiol Induces Reversible Alterations in Tuberoinfundibular Dopaminergic Neurons: a Decreased Responsiveness to Prolactin

Demarest

Riegle²,

Moore

1984

Neuroendocrinology

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“…There are only a few animal models available which are sensitive to dopamine agonists, such as the SMtTW tumor, a spontaneous prolactin-secreting transplantable tumor (4), and some studies using estrogen-induced hyperprolactinemia and pituitary enlargement (3,(11)(12)(13)(14)(15). These studies did not report which doses and duration of in vivo estrogen administration are required to promote prolactin hypersecretion without pituitary enlargement or if bromocriptine effects on prolactin levels and lactotroph proliferation may vary with different schedules of estrogen treatment.…”

Section: Mf Ribeiro Et Almentioning

confidence: 99%

Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

Ribeiro¹,

Spritzer²,

Barbosa-Coutinho³

et al. 1997

Braz J Med Biol Res

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The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradioltreated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat -1 week -1 ) for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat -1 day -1 ) was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05). Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats.

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“…Although the reasons for the sex difference not established conclusively, it probably results from abnormal exposure of females to estrogen (30,31). In addition to these pituitary effects, estrogen alters CNS monoamine metabolism as described above (32).…”

Section: Serotoninergic Drugs and Pituitary Neoplasmsmentioning

confidence: 99%

Age Factors Potentiating Drug Toxicity in the Reproductive Axis

Walker¹

1986

Environmental Health Perspectives

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Defective Central Nervous System Dopaminergic Function in Rats with Estrogen-Induced Pituitary Tumors, as Assessed by Plasma Prolactin Concentrations*

Cited by 70 publications

References 30 publications

Long-Term Treatment with Estradiol Induces Reversible Alterations in Tuberoinfundibular Dopaminergic Neurons: a Decreased Responsiveness to Prolactin

Long-Term Treatment with Estradiol Induces Reversible Alterations in Tuberoinfundibular Dopaminergic Neurons: a Decreased Responsiveness to Prolactin

Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

Age Factors Potentiating Drug Toxicity in the Reproductive Axis

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