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In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: Direct evidence for a dopaminergic principle by the dopamine receptor assay

Dept. Clinical and Experimental Endocrinology, University of Göttingen, Germany.
Experimental and clinical endocrinology 02/1994; 102(6):448-54. DOI: 10.1055/s-0029-1211317
Source: PubMed

ABSTRACT Women suffering from premenstrual mastodynia often respond to stimuli of prolactin (Prl) release with a hypersecretion of this hormone. Pharmacological reduction of Prl release by dopamine agonists or treatment with extracts of Agnus castus (AC) improve the clinical situation of patients with such premenstrual symptoms. Extracts of AC contain compounds which inhibit in vivo Prl release in women as well as in vitro from dispersed rat pituitary cells. It is yet unknown whether this inhibitory action of AC is only exerted on Prl release or whether release of other pituitary hormones like LH and FSH is also affected. The effects of AC on LH and FSH release were examined in vitro using rat pituitary cell cultures. To rule out that the Prl-inhibiting properties of AC are at least in part due to a cytotoxic component, pituitary cell cultures were subjected to the MTT test. To assess whether the Prl inhibitory effect of AC preparations is due to compounds acting as dopamine (DA) agonists, we used the corpus striatum membrane DA receptor binding assay. Our results demonstrate for the first time that AC extract contains an active principle that binds to the D2 receptor. Thus, it is very likely that it is this dopaminergic principle which inhibits Prl release in vitro from rat pituitary cells. Furthermore we give evidence for the specificity of action of AC on hormone release, since gonadotropin secretion remained unaffected. The findings of the present study support the therapeutical usefulness of AC extracts for treatment of premenstrual mastodynia which is associated with hypersecretion of Prl. Furthermore, the beneficial effects of AC appear to be due to the inhibition of pituitary Prl release.

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    • "In our research, Casticin had shown analgesic effects and reduced abnormally high serum prolactin levels. In a study of the extract of V. agnus castus (CA), using the corpus striatum membrane dopamine (DA) receptor binding assay in vitro, however , diterpenes (not Casticin) were reported as the active constituents, acting as DA agonists and inhibiting the release of prolactin (Jarry et al., 1994; Berger et al., "
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    ABSTRACT: Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p < 0.01). Using bioassay-screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).
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    • "Several studies have indicated that VAC acts on dopamine D2 receptors to decrease prolactin levels (Jarry et al., 1994; Hoberg, 1999; Berger et al., 2000; Meier et al., 2000; Wuttke et al., 2003). This mechanism is most likely responsible for alleviating symptoms of mastodynia and hyperprolactinemia (Milewicz et al., 1993; Meier and Hoberg, 1999). "
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    • "Many premenstrual symptoms, particularly premenstrual mastalgia (mastodynia) are associated with latent hyperprolactinemia (Jarry et al. 1994; Wuttke et al. 1997; Jarry et al. 1999). These patients do not suffer from prolactinomas but in response to daily stressful events they hypersecrete prolactin which appears to stimulate the mammary gland thereby causing "
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