Elevation Of Plasma Prolactin Concentration Research Articles

The effect of 6-hydroxydopamine infusion into the third cerebral ventricle on the plasma prolactin levels in anoestrous ewes subjected to prolonged and repeated stress.

The effect of 6-hydroxydopamine (6-OHDA) infusion into the third cerebral ventricle on the secretion pattern of prolactin in anoestrous sheep, subjected to repeated and prolonged stress-stimuli was followed. On the 12-15 th day after the infusion of 6-OHDA into the third cerebral ventricle and after having tested the effect of this infusion on plasma prolactin concentration, the animals were subjected to mild electric footshocks 9 hrs daily (9 a.m.-6 p.m.) for 3 consecutive days. Infusion of 6-OHDA induced a very high rise of plasma prolactin values by about 3 times as compared to those found before infusion (from 118.2 +/- 39.5 to 338.9 +/- 81.7 ng/ml mesor 24 h). On the other hand, the response of the animals pretreated with 6-OHDA to electric stimulation was characterized by the lack of changes in plasma prolactin concentration; their plasma hormone concentrations were neither raised during stimulation nor decreased after the stimulation and were maintained during all these days nearly at the same level as after the infusion of 6-OHDA. Central mechanisms which could account for the so high and prolonged elevation of plasma prolactin concentration after the infusion of 6-OHDA and for the lack of its rise under conditions of prolonged stress are discussed.

Ziprasidone: a review of its use in schizophrenia and schizoaffective disorder.

Ziprasidone is a novel antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical antipsychotics. In preclinical studies, ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. The drug has been administered orally to >300 patients with an acute exacerbation of schizophrenia or schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily, at dosages of between 80 and 160 mg/day, ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study, ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day. Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic schizophrenia who were treated for up to 1 year. In addition, significantly more ziprasidone than haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic schizophrenia. In general, oral ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the drug has a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The drug does not appear to be associated with sustained elevation of plasma prolactin concentrations. Preliminary data indicate that long-term oral ziprasidone treatment is well tolerated. Ziprasidone is the only novel antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular ziprasidone was effective and well tolerated in patients with acute agitation associated with psychosis. In addition, intramuscular ziprasidone reduced agitation scores by a significantly greater extent than haloperidol in a study involving patients with acute agitation associated with psychosis. Ziprasidone is a promising new antipsychotic that has shown significant efficacy in the oral treatment of patients with schizophrenia or schizoaffective disorder. The drug is well tolerated with a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and good tolerability in the treatment of acute agitation associated with psychotic disorders.

Elevation of Plasma Prolactin Concentrations by Low Temperature Is the Cause of Spermatogonial Cell Death in the Newt,Cynops pyrrhogaster

Temperature plays an important role in reproduction of urodeles. Spermatogenesis in newts is arrested when the environmental temperature lowers. We found that transfer of newts,Cynops pyrrhogaster,to low temperature (8 and 12°C) caused cell death of spermatogonia just before meiosis and elevation of prolactin concentration in the newt plasma. Injection of a dopamine antagonist (pimozide), which is known to increase the plasma prolactin concentration, to the newt caused significant increase of spermatogonial degeneration, whereas treatment with an agonist (bromocryptin), which is known to decrease the prolactin concentration, suppressed the cell death. Finally, injection of anti-prolactin serum into the newts which had been transferred to low temperature almost completely inhibited the spermatogonial degeneration for as long as 3 days. These results demonstrate that low temperature caused elevation of prolactin concentration in the newt blood, which induced cell death of spermatogonia just before meiosis.

Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats.

1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of piracetam were tested (20, 100, 200 and 400 mg kg-1), being given intraperitoneally 1 h before blood sampling; control rats received saline instead. After a first blood sample, rats were subjected to immobilization stress and received morphine, 6 mg kg-1, 90 min later. 3. Piracetam had no effect on basal plasma PRL concentration. 4. While in the non-piracetam-treated rats, stress produced a significant rise in plasma PRL concentration, in the piracetam-pretreated rats PRL peaks were attenuated, especially in the group given 100 mg kg-1 piracetam, where plasma PRL concentration was not significantly different from basal values. The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise. 5. In unrestrained rats, morphine led to a significant elevation of plasma PRL concentration. After the application of immobilization stress it lost its ability to raise plasma PRL concentration in the control rats, but not in the piracetam-treated rats. This tolerance was overcome by piracetam in a significant manner but with a reversed dose-response curve; i.e. the smaller the dose of piracetam, the higher the subsequent morphine-induced PRL peak. 6. There is no simple explanation for the mechanism by which piracetam induces these contradictory effects. Interference with the excitatory amino acid system, which is also involved in opiate action, is proposed speculatively as a possible mediator of the effects of piracetam.

The role of prolactin in the reactivation of hair follicles in relation to moulting in cashmere goats.

The effects of the suppression or elevation of plasma prolactin concentrations in spring on the timing of the reactivation of the hair follicles and the timing of the spring moult were investigated in cashmere goats. Thirty eight adult female goats, housed under conditions of natural photoperiod at 55 degrees 55'N from mid-December until May, were allocated to four groups starting on 5 January: ten served as untreated controls, eight received 2 mg ovine prolactin subcutaneously every 12 h for 7 weeks (PRL), twelve received 35 mg bromocriptine intramuscularly every 14 days for 17 weeks (BCR) and eight received injections of both ovine prolactin and bromocriptine at the above dose rates for 7 weeks (PRL+BCR). In the PRL group there was an earlier reactivation of the secondary hair follicles (PRL vs control, proportion of secondary follicles in antigen, weeks 1-5, P < 0.01) associated with an earlier moult of secondary fibres (cashmere) but no significant difference in the activity of the primary hair follicles. In the BCR group there was a delay in the reactivation of both the secondary and primary hair follicles (BCR vs control, proportion of secondary and primary hair follicles in anagen, weeks 5-13, P < 0.01) and a delay in the moult. In the PRL+BCR group there was an early reactivation and moult similar to the PRL group. Voluntary food intake (VFI) and liveweight were also measured. Only in the BCR group was there a decrease in VFI compared with the controls but with no effect on liveweight.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations between presence of spontaneous lesions of the pituitary (adenohypophysis) and plasma prolactin concentration in aged Wistar rats.

The predictive value of elevated plasma prolactin concentrations for the presence of spontaneous pituitary lesions was studied in 40 male and 38 female Wistar (Cpb:WU) rats, all 30 months old. The pituitaries were examined light microscopically and stained for prolactin using immunohistochemical methods. Plasma prolactin concentrations were measured by radioimmunoassay. Pituitary lesions were classified on the basis of their morphology in hematoxylin and eosin-stained sections as foci of hypertrophic or hyperplastic cells and hemorrhagic, pleomorphic, or spongiocytic adenomas; no carcinomas were found. There were significantly (P = 0.001) more female than male rats with pituitary adenomas (58% females, 33% males) or without any pituitary lesions (21% females, 5% males); however, there were less female (21%) than male rats (63%) with foci of hyperplastic and/or hypertrophic cells but no adenomas in the pituitary (P = 0.001). Elevation of plasma prolactin concentration above the upper 99th percentile value in age-matched rats without lesions was predictive, but not conclusively, of the presence of pituitary hemorrhagic adenomas in both sexes. It was, however, not predictive of the presence of foci of hypertrophic or hyperplastic cells. Elevation of plasma prolactin concentration above 10 ng/ml in male and 60 ng/ml in female rats was conclusive for the presence of hemorrhagic adenomas. Using multivariate analysis, significant positive correlations (P less than 0.01) were found between plasma prolactin concentration and presence and size of hemorrhagic adenomas and their prolactin staining intensity (correlation coefficients between 0.392 and 0.652). Foci of hyperplastic cells stained positively for prolactin, whereas hypertrophic cell foci and pleomorphic and spongiocytic adenomas did not stain for prolactin. There were no correlations (coefficients of less than +/- 0.189) between plasma prolactin concentration and the presence of hypertrophic or hyperplastic cell foci and pleomorphic or spongiocytic adenomas in the pituitary. The morphologic criteria developed to distinguish spontaneous hypertrophic, hyperplastic, and neoplastic lesions of the rat pituitary corresponded well with their prolactin immunoreactivity and/or ability to elevate plasma prolactin concentration. These criteria constitute a biologically meaningful classification system for these rat pituitary lesions.

Elevation of plasma prolactin concentrations by intravenous SCH 23390 and SKF 38393 in conscious rats

The effect of the selective dopamine-1 (D-1) antagonist, SCH 23390 and the selective D-1 agonist, SKF 38393 on plasma prolactin levels was investigated in conscious, freely moving male rats. Plasma prolactin was markedly increased by the intravenous injection of either SCH 23390 or SKF 38393 in a dose-related fashion. The maximal prolactin response was observed 15 min after drug injection. The d-isomer of SKF 38393 was significantly more potent than the l-isomer. In urethane-anesthetized rats, the two drugs produced similar effects on prolactin as those in the conscious animal preparation. Both SCH 23390 and SKF 38393 potentiated the sulpiride-induced prolactin as those in the These observations suggest that pharmacologic stimulation, or blockade of D-1 receptors in the living animal, can mimic the action of a D 2 antagonist at the anterior pituitary lactotroph. We have speculated on the possible mechanisms in pituitary and higher in the central nervous system which might be responsible for the prolactin changes caused by either SCH 23390 of SKF 38393.

Gamma-aminobutyric acid is not likely a physiological prolactin-inhibiting factor.

Basal plasma prolactin concentration is controlled by tonic inhibition. The major prolactin-inhibiting factor (PIF) is believed to be dopamine. Factors other than dopamine have also been suggested as possible physiological PIF. One of the major candidates for the nondopaminergic PIF is considered to be gamma-aminobutyric acid (GABA). We have carefully examined the possible physiological role of GABA by monitoring, at every 2 min, the circulating prolactin concentration after GABA administration, in conscious freely moving rats. GABA (0.1 or 1 g/kg) had no significant direct effect on plasma prolactin in rats in which the dopaminergic receptors were completely blocked by pimozide, nor in hypophysectomized rats in which a pituitary had been grafted under the kidney capsule and was therefore removed from any hypothalamic influence. The effects of bicuculline, a GABA-receptor-blocking agent, was examined in order to find out whether a tonic inhibition is exerted by GABA after elimination of tonic dopaminergic inhibition on prolactin secretion. The pimozide-treated rat in which the dopaminergic tone is completely eliminated did not show any prominent elevation of plasma prolactin concentration after bicuculline (300 micrograms/kg) administration. However, GABA did have an inhibitory effect in a primary pituitary cell monolayer culture system. Therefore, we conclude that GABA does not play a significant role as a physiological PIF and that the inhibitory effect of GABA in vitro is of a pharmacological nature.

The role of the cholinergic system in controlling the nocturnal prolactin surge in pseudopregnant rats

To elucidate the role of the cholinergic system in controlling the nocturnal prolactin (PRL) surge in the early stage of rat pseudopregnancy, the effects of subcutaneous or intracerebroventricular (ICV) injections of various cholinergic agonists and antagonists on the pattern of the nocturnal PRL surge were investigated. Pseudopregnancy was induced by stimulating the uterine cervix with a vibrator between 0630 h and 0700 h on the morning of estrus (Day 0). Blood samples for PRL analysis by RIA were obtained every two hours from 2300 h on Day 2 to 0900 h on Day 3 through an indwelling venous cannula, which was implanted on Day 1 under pentobarbital-Na anesthesia, or by decapitation at 0300 h on Day 3. For ICV injection of the drug, rats were implanted with a stainless steel guide cannula 1.0 mm above the right lateral ventricle on diestrus 1 of the estrous cycle. They were given cervical stimulation on the initial estrous morning after the above operation. Control rats given saline solution showed a nocturnal PRL surge between 0100 h and 0700 h on Day 3 in the present study. Atropine sulfate (70 and 700 mg/kg) injected subcutaneously resulted in the complete inhibition of the nocturnal PRL surge whenever given at 2100 h on Day 2, 0000 h on Day 3 and 0300 h on Day 3, which corresponded to 4 hours and 1 hour before and 2 hours after the starting of the nocturnal PRL surge, respectively. ICV injection of atropine sulfate (250 micrograms/rat) also inhibited the occurrence of the nocturnal PRL surge when given at 0000 h on Day 3, though a slight and transient elevation of plasma PRL levels were seen. Subcutaneous injection of pilocarpine hydrochloride (5 and 50 mg/kg), a cholinergic agonist, did not affect the elevation of plasma PRL concentration observed at 0300 h on Day 3 when administered 3 hours before. The other agonist, arecoline hydrochloride, also did not affect the pattern of the nocturnal PRL surge when administered intravenously between 2315 h on Day 2 and 0515 h on Day 3. Subcutaneous injection of pimozide (1 mg/kg), a dopaminergic antagonist, just after the administration of atropine sulfate (700 mg/kg) given at 0000 h on Day 3 overcame the inhibitory effect of the later compound on the nocturnal PRL surge. However, the high levels of plasma PRL concentration still remained at 0700 h and 0900 h on Day 3 without any decrease as observed in the controls. These results suggest that the cholinergic system may be involved as a modulator in controlling physiological mechanism(s) of the nocturnal PRL surge in pseudopregnant rats.

Thyrotropin releasing hormone (TRH) is not the physiological prolactin releasing factor (PRF) in the male rat

Thyrotropin releasing hormone (TRH) is known to stimulate prolactin secretion but it is not known whether TRH is the physiological prolactin releasing factor (PRF) or whether the TRH effect on prolactin secretion is a pharmacological action. Normal male rats were implanted with permanent right atrial cannulae and sequential blood samples were taken every min through the cannula. Ether stress elevated plasma prolactin to more than 3 times the normal concentration, while plasma TSH was not changed. However, TRH raised plasma TSH to more than 5 times the normal concentration, while the elevation of plasma prolactin concentration was marginal. The dissociation between the elevation of plasma TSH and prolactin concentrations with ether stress and TRH injection indicates that TRH is not the physiological PRF.