Prolactin-inhibiting activity

Winterhoff, H., C. Gorkow, and B. Behr. 1991. Reduced lactation in rats following application of agnus-castus-extract An indirect evidence for the prolactin inhibiting activity. Ztschr. Phytother. 12(6) 175-179. 

RATNER, A., TALWALKER, P.K. and MEITES, J. Effect of reserpine on prolactin-inhibiting activity of rat hypothalamus. Endocrinology 315-319 1965. 

F. Prolactin-Inhibiting Hormone (PIH, Dopamine) Dopamine is the physiologic inhibitor of prolactin release. Because of its peripheral effects and the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia, but bromocriptine and other orally active ergot derivatives (eg, cabergoline. pergolide) are effective in reducing prolactin secretion from the normal gland as well as from pituitary tumors. 

Clemens, J.A., Okimura, T. and Smalstig, E.B. (1993) Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition. 

The lipidosterolic extract, in Chinese hamster ovary cells, reduced the basal activity of a K channel and of protein kinase (PK) C. Pretreatment of the cells with the extract for 6-36 hours abolished the effects of prolactin on Ca 3 K conductance and PKC. The results indicated that the extract can block prolactin-induced prostate growth by inhibiting several steps of prolactin receptor signal transduction . 

Chinese hamster ovary cells overexpressing the prolactin receptor, was active . Protein synthesis stimulation. Sterol fraction of the extract, in cell culture at a concentration of 25 (xg/mL, produced weak activity on CA-LNCAP. A concentration of 50 (xg/mL was active on CA-PC3 h PSA production inhibition. Ethanol (70%) extract of PC-SPES (a Chinese herb combination of chrysanthemum, dyers woad, licorice, reishi, san-qi ginseng, rabdosia, saw palmetto, and baikal skullcap), in cultured prostate cancer cell line at variable doses for 24 hours, produced a significant effect in supressing cell growth in all the cell lines h... 

Amoxapine has been found to be effective in several double-blind studies (Table 7-4 and Table 7-6). It is a dibenzoxazepine derivative that has both NE and serotonin uptake inhibiting properties. Amoxapine is converted into 8-hydroxyamoxapine, which has considerable dopamine receptor binding properties (i.e., radioreceptor bioassays on patients given amoxapine have found activity levels similar to those of patients on typical antipsychotics), a chemical structure similar to loxapine, and effects similar to antipsychotics (1Q3). As a result of this metabolite, amoxapine theoretically may have unique beneficial effects in psychotically depressed patients. However, this possibility has never been adequately tested. Nevertheless, this metabolite is likely responsible for some of the antidopamine effects reported in patients taking amoxapine, including acute and chronic extrapyramidal side effects and elevated prolactin levels ( 104). Like TCAs, amoxapine can be lethal in... 

The dopamine neurons that project from the hypothalamus to the anterior pituitary are known as the tuberoinfundibular dopamine pathway (Fig. 10—13). Normally, these neurons are active and inhibit prolactin release. In the postpartum state, however, their activity is decreased, and therefore prolactin levels can rise during breastfeeding, so that lactation will occur. If the functioning of tuberoinfundibular dopamine neurons is disrupted by lesions or drugs, prolactin levels can also rise. Elevated prolactin levels are associated with galactorrhea (breast secretions), amenorrhea,... 

The G protein-GTP complexes related to receptors for these hormones activate adenylyl cyclase, which synthesizes the second messenger cAMP. Cyclic AMP activates protein kinases, which phosphorylate certain intracellular proteins (eg, enzymes), thus producing the hormonal effect. Conversely, dopamine binding to lactotroph receptors causes conformational changes in its G protein that reduce the activity of adenylyl cyclase and inhibit the secretion of prolactin. 

The role of cyclic AMP as modulator of prolactin secretion was first suggested by the finding of a stimulatory effect of cyclic AMP derivatives (17-22) and inhibitors of cyclic nucleotide phosphodiesterase activity such as theophylline and IBMX (22-26) on the secretion of this hormone. More convincing evidence supporting a role of cyclic AMP in the action of dopamine on prolactin secretion had to be obtained, however, by measurement of adenohypophysial adenylate cyclase activity or cyclic AMP accumulation under the influence of the catecholamine. As illustrated in Fig. 1, addition of 100 nM dopamine to male rat hemipituitaries led to a rapid inhibition of cyclic AMP accumulation, a maximal effect (30% inhibition) being already obtained 5 min after addition of the catecholamine. Thus, while dopamine is well known to stimulate adenylate cyclase activity in the striatum (27, 28), its effect at the adenohypophysial level in intact cells is inhibitory. Dopamine has also been found to exert parallel inhibitory effects on cyclic AMP levels and prolactin release in ovine adenohypophysial cells in culture (29) and purified rat mammotrophs (30). Using paired hemipituitaries obtained from female rats, Ray and Wallis (22) have found a rapid inhibitory effect of dopamine on cyclic AMP accumulation to approximately 75% of control. 

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