Serum prolactin levels after seizure and syncopal attacks.

Loss of consciousness and falling are the key features of syncope. Common accompaniments include tonic and myoclonic muscle activity, eye deviations, automatisms, vocalizations and hallucinations that may render the distinction from epileptic seizures difficult. The frequently increased levels of serum prolactin (SPRL) were observed immediately after generalized and complex partial seizures. Presumably, the hormone release is caused by the propagation of epileptic activity, usually from the temporal lobe to the hypothalamic pituitary axis. Numerous reports have demonstrated that the post-ictal SPRL level may be used to differentiate between epileptic and syncopal, non-epileptic attacks. In order to confirm the hypothesis, the SPRL levels were measured in patients with complex partial seizures (CPS) and patients with vaso-vagal syncopal attacks (VVS). The SPRL levels were prospectively measured for each patient as soon as possible after the event (within 1 hour), then 1 hour after the first determination and finally blood was sampled 24 hours later. During the study period (18 months), 18 patients with CPS and 15 patients with VVS were investigated in total. The mean values of SPRL levels in both groups were increased immediately after the event (CPS group: 1142 +/- 305 mIU/l; VVS group: 874 +/- 208 mIU/l). The elevated SPRL levels were found in 14 (78%) patients immediately after CPS and in 9 (60%) patients immediately after VVS. After examining the results of the present study we conclude that the elevated serum prolactin level after an epileptic attack is of no significant value in differential diagnosis between epileptic and vaso-vagal syncopal attacks.     

Differential diagnostic value of postictal serum prolactin determination

Determination of serum prolactin concentration was carried out under standardized conditions on 70 hospitalised patients after different types of epileptic, syncopal and psychogenic seizures. In cases of unconsciousness of unknown cause and of unobserved seizures there is evidence that the determination of postictal prolactin may help to clarify the diagnosis. Excluding patients with epileptic seizures due to alcohol withdrawal only in 70% of the patients was there a significant elevation of serum prolactin. The clinical procedure thus appears to be of importance also in the differential diagnosis of psychogenic seizures. Patients with epileptic seizures due to alcohol withdrawal showed an elevated prolactin concentration in only 45% of cases. Whereas an elevated serum prolactin level indicates the occurrence of a grand mal seizure, a normal prolactin level does not positively exclude epileptic seizures.     

Effect of lactation on the expression of audiogenic seizures: association with plasma prolactin profiles

Female Wistar rats and Wistar audiogenic rats (WARs) were used to investigate the potential roles of prolactin (PRL) and progesterone in the modulation of seizure expression. Animals were screened for seizure severity in both groups. All WARs at least displayed tonic-clonic convulsions followed by clonic spasms (TC) whereas none of the Wistar rats displayed seizures (Resistant). After seizures the plasma level of PRL in nulliparous female WARs increased about 8-fold compared to their basal levels and to the levels of Resistant animals. This value was still significantly higher than basal levels 15 min later. Lactation produced a decrease in the TC proportion in seizures in WARs both with and without pups. Two sub-populations of animals could be characterized: one that had TC suppressed (low seizure severity; LSS) and one that did not (high seizure severity; HSS). In animals of the LSS subgroup, either with or without pups, seizure severity decreased gradually and lowest values were seen on the 30th day after delivery. The temporal profile of plasma PRL during a 90-min period of suckling without sound stimulation showed significantly higher levels for LSS, the HSS levels being similar to those of the Resistant group. A progressive decrease in the group means for progesterone plasma concentration between the 9th and 29th days of lactation was detected in Resistant rats (P<0.05) but not in WARs. No significant differences between groups were revealed by comparison of the overall means. Taken together these data confirm the presence of a clear-cut post-ictal PRL peak after TC with a decrease in seizure severity in female WARs with and without pups. An eventual long-term role of PRL in modulating seizure activity might be related to the multifactorial physiological conditions of both pregnancy and lactation.     

Serum prolactin response to repetitive epileptic seizures

We measured postictal prolactin (PRL) levels during repetitive seizures in 14 patients (10 men and 4 women) suffering from epilepsy with focal and/or secondarily generalized seizures. Between two and six seizures occurred per patient (mean 2.7). The interveral between seizures was 15 min and 8 h 40 min (mean 3 h 32 min). Five of the 14 patients showed a marked postictal PRL rise after each seizure (i.e. concentrations above 700 U/ml for women, 500 U/ml for men). In the remaining 9 patients there was no detectable rise in PRL. A decrease in PRL did not occur in any of the 14 patients. In those patients who had shown a marked PRL increase after the first seizure, the PRL continued to rise in subsequent seizures. Unlike previous investigations, these results show that repetitive epileptic seizures are not necessarily followed by a decrease in postical PRL levels. A decrease in PRL response is known to occur if there is progression to status epilepticus.     

Neuroendocrine responses to intravenous tryptophan in major depression

The increases in plasma levels of prolactin (PRL) and growth hormone (GH) following intravenous administration of the 5-hydroxytryptamine precursor tryptophan (100 mg/kg) were assessed in 30 depressed patients and 30 control subjects. In depressed patients who lost less than 10 lb, PRL responses were significantly reduced compared with controls. In contrast, the PRL responses of patients with weight loss exceeding 10 lb were significantly greater than those of either controls or the other depressed patients. Growth hormone responses to tryptophan were significantly decreased in patients who lost less than 10 lb. Prolactin, but not GH, responses correlated significantly with the postdexamethasone plasma cortisol concentration; however, an apparent relationship between GH and PRL responses and suicidal behavior was probably due to the common factor of weight loss. The results suggest that depressed patients have different types of abnormal 5-hydroxytryptamine-mediated neuroendocrine responses that correlate with the presence or absence of severe weight loss and cortisol hypersecretion. Further investigations are needed to establish if these abnormalities are central to the depressive disorder or have implications for treatment response.     

The effect of epileptiform discharges on neurohormonal release in epileptic patients with complex partial seizures

We compared the nocturnal plasma prolactin (PRL) and beta-endorphin (B-E) concentrations prior to and after sleep deprivation (SD) in eight epileptic patients with complex partial seizures. After the period of SD (1) the mean number of interictal epileptiform discharges and the mean plasma PRL levels showed a significant rise during light non-REM stages of sleep, and (2) mean nocturnal plasma PRL and B-E concentrations showed a moderate rise during the first few hours of sleep, significant only for plasma PRL. In a patient with multiple complex partial seizures during sleep, the levels of plasma PRL and B-E concentrations were closely related to ictal discharges. The data obtained in this stress-free environment suggest a centrally mediated interaction between the release of PRL and B-E, in relation to epileptic discharges.     

Lack of tolerance to long-term neuroleptic treatment in dopamine tuberoinfundibular system

The plasma prolactin (PRL) levels of 35 chronic schizophrenic patients undergoing long-term maintenance treatment with neuroleptic drugs were measured before and after either neuroleptic withdrawal or a switch to a fixed dose of chlorpromazine 900 mg/day. In both men and women there tended to be a significant correlation between the initial log plasma PRL level while on neuroleptic maintenance treatment and the dosage received converted to chlorpromazine equivalents. Neuroleptic withdrawal in ech of 19 cases was followed by a decline in PRL plasma levels. Switching to chlorpromazine 900 mg/day (16 cases) produced either increases or decreases in PRL plasma levels that were significantly correlated with the change in neuroleptic dosage converted to chlorpromazine equivalents. Thus there was no evidence of tolerance to the PRL-elevating effect of neuroleptics in these patients who had been treated for many years with neuroleptics.     

Dopaminergic factors in human prolactin regulation: Effects of neuroleptics and dopamine

(1) We have recently suggested that the plasma prolactin (PRL) response to the administration of a neuroleptic drug may serve as a measure of dopaminergic blockade in man. (2) In four normal men the PRL concentration remained elevated above baseline for at least seven hr following a single i.m. administration of haloperidol 1 mg; this is consistent with reported data on the plasma half-life of haloperidol. (3) With six normal men as their own controls, dose-PRL response curves of haloperidol, prochlorperazine and thiothixene were shown to be essentially parallel, suggesting a common antidopaminergic mechanism of action when releasing PRL. (4) In two studies, dopamine hydrochloride was infused at a constant rate of 0.3 mg/min; the DA infusion was started either immediately after a neuroleptic had been given i.v. or 30 min later. In the first study DA totally antagonized the neuroleptic induced PRL response; in the second study DA suppressed the neuroleptic-induced high PRL concentration to baseline level within one hr. (5) These findings provide further support for the hypothesis that the PRL response to a neuroleptic is a valid test of dopaminergic blockade in man.     

Factors influencing prolactin release induced by electroconvulsive therapy

Electroconvulsions have been reported to induce rapid elevations of serum prolactin (PRL) levels. To further evaluate factors involved in the hormonal release an extended study was performed. Blood samples for determination of PRL were withdrawn from depressed patients 5 min before and 15 min after administration of electroconvulsions. Significant elevations of PRL levels were found in 35 of 37 patients. Increase in PRL levels was significantly correlated to duration of seizures but not to duration of the electric stimulation. The hormonal response to electroconvulsions was diminished with age. Patients on lithium medication had significantly more pronounced rises of PRL levels than patients treated with other psychotropic drugs and otherwise untreated patients. The results indicate that the elevation in PRL levels is a biochemical marker of the seizure activity during electroconvulsive therapy.     

Effect of Interictal Epileptiform Discharges on Nocturnal Plasma Prolactin Concentrations in Epileptic Patients with Complex Partial Seizures

To investigate the effect of interictal epileptiform discharges (IEDs) on plasma prolactin (PRL) level, we studied 18 epileptic patients with complex partial seizures (CPS) who did not experience clinical or subclinical ictal events during all-night monitoring with polygraphic recording and video imaging. The density of IEDs peaked during non-REM stages and was significantly reduced during REM stage. Mean plasma PRL concentrations in epileptic patients, when sampled at 30-min intervals, showed a moderate but significant elevation during non-REM (p less than 0.001) and awake stages (p less than 0.005), but not during REM stage, when compared with 10 nonepileptic control subjects studied in a similar fashion. The data obtained in this physiologically controlled environment indicate that the cumulative effect of IEDs may modify PRL regulatory mechanisms, resulting in a modest elevation of plasma concentrations independent of ictal discharges.     

Effect of estradiol and progesterone on rat striatal dopamine uptake sites

Striatal dopamine (DA) uptake sites labelled with [3H]GBR-12935 binding were investigated in ovariectomized (OVX) rats acutely treated with 17 beta-estradiol (E2) or progesterone (P). One injection of E2 (100 ng, SC) to OVX rats increased plasma levels of this steroid after 15 min while plasma prolactin (PRL) levels remained unchanged. The E2 injection left striatal [3H]GBR-12935 binding affinity unchanged while the maximum density increased 15 and 30 min after the injection (+24% and +18%, respectively). One injection of P (110 micrograms, SC) to OVX rats increased this steroid plasma level from 15 to 120 min while plasma PRL levels remained unchanged. [3H]GBR-12935 binding density and affinity remained unchanged up to 120 min after the injection. Thus, acutely, E2 but not P, modulated striatal DA uptake sites in OVX rats. The effect of E2 appeared in coincidence with the peak of this steroid plasma concentration. This increase was rapid and is probably nongenomic and suggests a causal effect relationship as well as a presynaptic site of action of E2.     

Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements during maintenance haloperidol treatment in male patients with schizophrenia.

Measurement of plasma prolactin (PRL) concentration and plasma homovanillic acid (HVA) concentration was performed in 24 patients with schizophrenia during maintenance haloperidol treatment. A significant inverse correlation was found between plasma PRL and ratings of both dyskinesia and thought disorder. Plasma PRL was also correlated with negative symptoms. No relationship was found between plasma HVA and any symptom grouping. Twelve patients received an apomorphine challenge; a trend toward a significant inverse relationship was found between baseline dyskinesia and apomorphine-induced decreases in plasma PRL. Plasma PRL and plasma HVA may reflect different elements of dopamine function in the central nervous system during maintenance treatment; plasma PRL may be the useful marker under these conditions.     

Evoked visual responses in schizophrenic patients]

The authors investigated during prolonged ambulatory treatment with the neuroleptic preparation isofloxythepine (IFT) changes of visually induced responses in 24 psychotic patients. The reference group was formed by 10 healthy volunteers examined before and after administration of a single dose of IFT by the oral route. In addition to the visually induced responses the authors investigated also plasma prolactin levels (PRL). It was found that the latency of the P1 peak and amplitude between peaks A1 are in psychotic patients altered, as compared with healthy subjects. The latency of the P1 peak is after a single dose of IFT in healthy subjects longer and the amplitude A1 higher than in the sick group. In healthy subjects after administration of IFT a negative correlation was observed between the amplitude and the basal PRL level. In patients no relationship was found between PRL levels and parameters of the visually induced response.     

Evidence of prolactin immunoreactivity in the bone marrow of untreated multiple myeloma patients

The role of prolactin (PRL) in the physiological regulation of the immune system and in hematopoiesis is well known. There is also evidence of the significance of PRL in several pathological conditions such as autoimmune diseases and some malignancies, e.g. colon and breast carcinomas and also B cell malignancies. Multiple myeloma is known as a B cell malignancy. It is the result of malignant transformation of a single clone of neoplastic plasma cells that synthesize abnormal amounts of monoclonal immunoglobulins or immunoglobulin fragments. In our present studies, the possible expression of PRL in bone marrow cells obtained from diagnosed multiple myeloma (17 cases) or nonmyeloma (5 cases) patients was examined by the method of immunocytochemistry. Samples obtained from those multiple myeloma patients (13 cases) who had not received chemotherapy for 6 months prior to these studies showed a positive immunocytochemical reaction for PRL. Bone marrow smears of patients diagnosed with multiple myeloma who had received chemotherapy within 6 months of the study and also the smears of patients without diagnosed multiple myeloma failed to show a positive immune reaction for PRL. In the case of a patient who was examined prior to and also after a period of 3 months of chemotherapy, the PRL-immunopositive bone marrow cells had disappeared due to the treatment. According to the light microscopic analysis of the cell morphology, PRL-immunopositive cells in the bone marrow were mainly, but not exclusively, plasma cells. There was no correlation between the positive PRL staining of cells and the type of monoclonal immunoglobulin or the ratio of plasma cells detected in the bone marrow. Taken together, our results indicate a possible role of PRL in multiple myeloma. Further experiments are necessary to identify the prognostic value of PRL in multiple myeloma.     

多巴胺D2受体基因Taq1A多态性与利培酮、帕利哌酮所致高泌乳素血症的关系

目的:探讨多巴胺2(D2)受体基因Taq1A多态性与利培酮、帕利哌酮所致高泌乳素血症(HPRL)的关联性。方法:92例女性精神分裂症患者给予利培酮或帕利哌酮治疗4周,于治疗前后测定血清PRL水平及治疗后的9-羟利培酮血药浓度;并检测所有受试者的D2受体基因Taq1A多态性。结果:HPRL组(治疗后PRL水平≥3 500 m IU/L者,n=30例)与LPRL组(治疗后PRL水平3 500m IU/L者,n=37例)Taq1A基因型等位基因频率组间差异无统计学意义(χ~2=1.73,P=0.42);Taq1A 3种基因型(A1/A1,A1/A2及A2/A2)患者血清PRL水平治疗后均明显增高,但治疗前后差值比较,组间差异无统计学意义(F=1.40,P=0.26)。结论:未发现D2受体基因Taq1A多态性与利培酮、帕利哌酮所致HPRL存在关联。     

Differential Response of Growth Hormone, Cortisol, and Prolactin to Seizures and to Stress

Plasma concentrations of growth hormone (GH), cortisol, and prolactin (PRL), following a spontaneous generalized seizure in epileptic men were compared with similar measurements made in nonepileptic, stressed men to determine the role of stress in the hormonal response to seizures. Nonepileptic, nonstressed men served as control subjects. GH concentrations increased significantly within 60 min postictally, and as expected, so did cortisol and PRL. A subgroup of alcoholic patients exhibited a smaller GH response to seizures. Stressed patients had significantly less elevated cortisol and PRL plasma values, but no rise of GH. The data suggest that neurogenic stimuli responsible for the postictal release of GH, cortisol, and PRL are, at least in part, independent of stress mechanisms and that GH response is blunted in alcoholic patients.     

Nocturnal plasma prolactin and cortisol levels in epileptics with complex partial seizures and primary generalized seizures

The nocturnal pattern of plasma prolactin (PRL) and cortisol in male epileptics with complex partial seizures and primary generalized seizures was studied by all-night polygraphic recordings with continuous video monitoring and sequential blood sampling at 30-minute intervals. Mean nocturnal plasma PRL concentrations in both groups of epileptics were significantly elevated when compared with nonepileptic control subjects studied in a similar fashion. Eight subclinical and three clinical partial seizures were recorded during sleep. Although a tenfold increase of plasma PRL level occurred following a short brief clinical complex partial seizure, there was no direct correlation between single subclinical partial seizures and nocturnal fluctuations of plasma PRL concentrations. We did not observe recognizable plasma cortisol changes following partial seizures during sleep, nor significant differences of mean nocturnal plasma cortisol levels between epileptics and controls. The data obtained in this environmentally controlled study indicate that postictal elevation of plasma PRL is a specific phenomenon related to seizure discharges; however, failure of such a rise does not exclude partial seizures.     

Neuroendocrine disorders observed in the post-critical phase in epileptic patients

In 10 epileptic patients with generalized seizures, plasma levels of ACTH, prolactin, FSH, LH, TSH, were measured first within 60 minutes after the crisis, then 3 to 5 days later without changes in antiepileptic drugs. Within 1 hour after the seizure, a significant rise of ACTH and prolactin 3 - 4 folds the levels observed in the 2nd measure was present. This was compared to measures made within 1 hour after a syncope in which case it was not present. The post-critic rise of ACTH and prolactin would appear to be a characteristic of generalized epileptic seizures.     

Plasma cortisol, prolactin, growth hormone, and immunoreactive beta-endorphin response to fenfluramine challenge in depressed patients

The effect of a single dose (60 mg p.o.) of the serotonin agonistic agent fenfluramine (FNF) on plasma cortisol, prolactin (PRL), growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) levels was assessed in eight major depressed patients and eight controls. The hormones were monitored at basal level (0') and hourly during 5 h following FNF administration. The pharmacological challenge caused an elevation of 80% in PRL secretion in the healthy controls and only 42% in the depressed patients. However, the actual prolactin response (delta max) failed to discriminate depressed patients from controls. A blunted response followed by a decrease (33%) in serum cortisol levels was observed in depressed patients 5 h after drug administration while an increase of 94% was obtained in controls after 3 h. FNF provocation did not affect GH and ir-beta-EP plasma levels. The blunted cortisol responsiveness to FNF administration in depressed patients may reflect functional hypoactivity of central serotonergic system at least during the acute phase of major depression. It is not clear why the cortisol hyporesponsivity in depressed patients is not accompanied by a similar reduced PRL response to FNF challenge.     

Lower prolactin bioactivity in unmedicated schizophrenic patients.

In previous work, prolactin (PRL) abnormalities of a lower bioassay (BA) to radioimmunoassay (RIA) ratio were found in schizophrenic patients. This line of research was extended in seven male patients with schizophrenia who were neuroleptic-free; seven male control subjects were also studied. PRL values were assessed by RIA and Nb(2) BA techniques. The schizophrenic group had a significantly lower PRL BA as compared to normal controls and a lower PRL ratio of BA/RIA. The lower ratio is consistent with an earlier finding and suggests that schizophrenic patients have different molecular forms of PRL than control subjects. This difference could be due to a disordered tuberoinfundibular dopamine system or the long-term effects of neuroleptic medications.