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

Ribeiro, Maria Flávia Marques; Spritzer, Poli Mara; Barbosa-Coutinho, Lígia Maria; Oliveira, Miriam C.; Pavanato, María A.; Silva, I.S.B.; Reis, Fm

doi:10.1590/s0100-879x1997000100017

Cited by 12 publications

(4 citation statements)

References 16 publications

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“…Prolactin levels in E 2 ‐induced rats were lower than published results , which could be attributed to the time of day of the experiment and E 2 dose. Caligaris et al .…”

Section: Discussioncontrasting

confidence: 79%

“…As expected, treatment with the centrally acting D2 receptor agonist bromocriptine inhibited E 2 ‐induced prolactin release, which is similar to previous finding that 1 mg/kg (iv) bromocriptine inhibited prolactin release and was similar to Ribiero et al . in that bromocriptine inhibited prolactin release in E 2 ‐treated ovariectomized rats. In addition, bromocriptine did not induce a rapid and transient prolactin increase in the current studies.…”

Section: Discussionmentioning

confidence: 87%

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Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

Brott

Werkheiser

Campbell

et al. 2012

Basic Clin Pharma Tox

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Centrally acting dopamine agonists (e.g. bromocriptine) and dopamine transport inhibitors (e.g. GBR12909) are known to inhibit oestradiol-induced prolactin release. The capacity of peripherally restricted compounds to do likewise, however, is unknown. Here, the effects of the peripherally restricted dopamine receptor agonist carmoxirole on oestradiol-induced prolactin release were investigated. Dual-cannulated ovariectomized rats were used, so that a robust, reproducible response to exogenous oestrogen could be induced and sequential blood samples were taken with minimal stress. Carmoxirole (15 mg/kg) inhibited oestradiol-induced prolactin release, similar to bromocriptine and GBR12909. However, carmoxirole also induced a rapid, transient, oestradiol-independent release of prolactin. These data show that peripherally restricted dopamine receptor agonists are sufficient to inhibit oestradiol-induced prolactin release. Like centrally acting compounds, they may therefore be expected to affect the incidence of prolactin-dependent tumours in rat carcinogenesis studies without inducing central-mediated side effects.Understanding the relevance or translation of pre-clinical drug effects to the clinic is critical for accurate human risk assessment for new pharmaceutical agents. In particular, accurate identification of specific mechanisms of serious toxicities observed in non-clinical species, and translation of specific mechanism in human beings can provide a scientific basis with which to evaluate specific risk in human beings. For example, it is known that some endocrine modulators can affect the incidence of particular tumours in life-time rat carcinogenicity bioassays, but not in human beings [1]. More specifically, the centrally active dopamine (D2) receptor agonist, bromocriptine, can induce hypoprolactinaemia in rats and human beings, but increases the incidence of hyperplastic proliferative endometrial lesions and benign and malignant uterine tumours only in rats [2], which has been postulated to be due to a lesser impact of prolactin on ovarian steroidogenesis in human beings [3].Prolactin is a peptide hormone spontaneously produced and secreted by lactotrophs in the anterior lobe of the pituitary gland under control by hypothalamic factors. In the rat, three dopaminergic systems [tuberoinfundibular (TIDA), tuberohypophyseal and periventricular hypophyseal dopaminergic neurons] regulate prolactin release, with the relative contribution varying between reproductive, physiological and pathological stages [4]. Hypothalamic dopaminergic neurons play a central role in the regulation of prolactin release by exerting an effect on the lactotrophs via the D2 receptor [5,6]. However, dopamine can also affect prolactin secretion by acting in the hypothalamus [7,8]. The pituitary lactotroph population is not entirely homogenous; mammosomatotropes, which are particularly common in neonatal rats, are differentiated into lactotrophs under the influence by oestrogens and secrete both prolactin and growth hormone [9]...

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“…Prolactin levels in E 2 ‐induced rats were lower than published results , which could be attributed to the time of day of the experiment and E 2 dose. Caligaris et al .…”

Section: Discussioncontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 87%

Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

Brott

Werkheiser

Campbell

et al. 2012

Basic Clin Pharma Tox

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“…In contrast, rats treated with 300 μg estradiol valerate showed a significant increase in the number of prolactin cells ( P < 0.05) ( Ribeiro et al., 1997 ). Estradiol valerate is a naturally or synthetically produced steroid and sold in brand names like Prygnova, Delestrogen, Prygnon depot ( Di Paolo et al., 1982 ).…”

Section: Introductionmentioning

confidence: 99%

The therapeutic effect of bromocriptine as mesylate and estradiol valerate on serum and blood biochemistry of common quails

et al. 2022

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Hematology and serum biochemistry study may provide antique knowledge about the physical status of individuals, making them a valuable tool to differentiate healthy animals from affected animals. We aimed to investigate Steroid safety levels in birds through ex-situ studies at regular therapeutic doses. A total of 100 birds were used for hematology and serum biochemistry. This study was designed into 2 trials over the summer and winter, each comprised 5, 10, 15, and 20 d. Each study group was based on 5 control group birds and 20 experimental group birds. A sum of 2 groups representing 2 different steroids trial groups was treated with therapeutic doses to the stretch of 5, 10, 15, and 20 d each season. A therapeutic dose of each of the steroids was given at the rate of 3 drops 2 times a day to each bird. Analysis of data reveals that steroids had severe effects on bird's (Coturnix coturnix) hematological parameters. In most trials, the hematological effects of bromocriptine as mesylate showed an increase in red blood cell count and white blood cell count. On the other hand, steroid estradiol valerate showed a decrease in these parameters. Effect of steroids on serum biochemistry profile indicate acute damage to vital organs, especially to liver and kidney, indicating an increase in cholesterol, total protein, albumin, urea, and uric acid. The overall effect of steroids on the bird's serum and biochemistry of quails were nearly similar but different only in their intensity.

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“…Working with an animal model previously established in our laboratory [2,3,10,32] we used estrogen-treated ovariectomized (OVX) female Wistar rats to investigate the ability of estrogen to modify the effect of p-chlorophenylalanine (pCPA), an inhibitor of 5-HT synthesis, on prolactin secretion. Therefore, the aims of this study were: 1) to determine the effects of pCPA in hypo-, normo-or hyperestrogenic states and 2) to investigate whether pCPA-induced prolactin secretion in estradiol-treated rats is associated with changes in dopaminergic and/or opioid systems.…”

Section: Introductionmentioning

confidence: 99%

Effect of Serotonin Depletion by p-Chlorophenylalanine on Serum Prolactin Levels in Estrogen-Treated Ovariectomized Rats: Insights Concerning the Serotoninergic, Dopaminergic and Opioid Systems

Mallmann

Ribeiro²,

Spritzer³

2001

Horm Metab Res

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The stimulatory effect of serotonin on prolactin secretion is well documented, and the administration of an inhibitor of serotonin synthesis (p-chlorophenylalanine - pCPA) has the expected inhibitory action on prolactin release in most experimental situations. However, there is evidence that in certain physiological or experimental conditions, activation of the serotoninergic system can also determine inhibition of prolactin secretion. The aim of the present study was to investigate the ability of estrogen to modify the effect of pCPA on prolactin secretion and to evaluate the participation of opioid and/or dopaminergic systems in regulating pCPA-induced prolactin secretion in estradiol-treated rats. We observed that pCPA administration (200 mg/kg/day, s.c., 2 days) to ovariectomized (OVX) female rats treated with estradiol benzoate (300 microg/week for 2 weeks, or 50 microg/week for 4 weeks, s.c.) causes a significant increase in serum prolactin, whereas no effect is observed in intact rats or in OVX rats without treatment. Bromocriptine administration completely reversed prolactin values previously increased by estradiol and by pCPA [OVX rats + estradiol = 86.50 ng/ml (68.90-175.02), OVX + estradiol + pCPA = 211.30 ng/ml (142.03-311.00), OVX + estradiol + pCPA + bromocriptine = 29.35 ng/ml (23.01 - 48.74), p<0.05. Naloxone administration partially reduced estrogen-induced high prolactin concentrations, but did not affect prolactin secretion stimulation determined by pCPA. Overall, the data from this report confirm the involvement of the dopaminergic system and, to a lesser degree, of endogenous opioids in prolactin secretion stimulation determined by estradiol. Furthermore, our results suggest that the stimulatory action of pCPA on prolactin secretion in estradiol-treated OVX rats is mediated by serotonin, which may also act indirectly on dopamine neurons.

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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

Cited by 12 publications

References 16 publications

Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

Inhibition of Oestradiol‐induced Prolactin Release in a Dual‐Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

The therapeutic effect of bromocriptine as mesylate and estradiol valerate on serum and blood biochemistry of common quails

Effect of Serotonin Depletion by p-Chlorophenylalanine on Serum Prolactin Levels in Estrogen-Treated Ovariectomized Rats: Insights Concerning the Serotoninergic, Dopaminergic and Opioid Systems

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