Serum Prolactin Response Research Articles

The coexistence of newly diagnosed acromegaly with primary empty sella: More frequent than expected?

ObjectiveWe investigated the coexistence of newly diagnosed acromegaly with primary empty sella (ES), which is considered to be a rare association, and the impact of ES on the laboratory, radiological and prognostic status of acromegaly. DesignAcromegaly patients diagnosed and followed-up between 2012 and 2021 were included. Empty sella was defined as the pituitary gland and adenoma filling <50% of the sella turcica on preoperative T1 magnetic resonance imaging (MRI). Results102 acromegalic patients (45 male, 57 female, 45.5 ± 12.8 (range: 20–70 years) were included and data of a median 3 years (range: 0.5–9 years) were presented. ES was detected in 19 (18.6%) patients and 4 had complete and 15 had partial ES. Although not significant, adenoma size and residual adenoma on MRI on postoperative 3rd month, and disease remission at last control were lower in acromegaly with ES than in acromegaly without ES, while the rate of female gender and remission on postoperative 3rd month were higher. While preoperative serum prolactin and nadir GH responses to OGTT were significantly lower in patients with ES, there was no difference in terms of other pituitary hormones among both groups. ConclusionThe present study revealed the coexistence of newly diagnosed acromegaly with primary ES at a rate of nearly 20% which is more frequent than expected and this association is not rare. The presence of ES was not associated with any preoperative/postoperative pituitary hormone levels and remission status, except lower preoperative prolactin and nadir GH responses to OGTT.

An unusual case of Cushing's syndrome due to bihormonal ACTH–prolactin secreting pituitary macroadenoma with rapid response to cabergoline

A 23-year-old man presenting with florid Cushing's syndrome was found to have high plasma ACTH and very high serum prolactin. Pituitary MRI showed a large invasive macroadenoma. Low-dose cabergoline promptly...

Relation between serum prolactin levels and antipsychotic response to risperidone in patients with schizophrenia

BackgroundHyperprolactinemia is commonly seen in patients with schizophrenia on risperidone. Dopamine receptor blockade plays a major role in risperidone induced hyperprolactinemia. However, limited studies are available with inconsistent results on antipsychotic response to risperidone and prolactin elevation. Therefore, we aimed to study the change in serum prolactin levels and response to risperidone and to test the association between DRD2 genetic variants and prolactin levels in schizophrenic patients treated with risperidone. MethodsA prospective study comprising of 102 patients with schizophrenia were recruited. Prolactin levels and Positive and Negative Syndrome Scale (PANSS) score were recorded at baseline and after four weeks of risperidone treatment. Prolactin concentrations were measured by standard method Advia-Centaur® Chemiluminescence immuno assay method. Taq1A DRD2 genotyping was performed by qRT-PCR. ResultsThe mean±SD prolactin levels (ng/ml) were increased after four weeks of treatment in both responders (males 21.66±15.15 to 41.63±18.73; p<0.01 females 51.92±40.89 to 122.35±52.16; p<0.01) and non-responders group (males 23.89±14.85 to 37.45±13.5; p<0.01 females 39.25±26.94 to 91.13±54.31; p<0.01). Patients with increased prolactin concentration were 4.6 fold higher in responders (OR 4.60; 95%CI 1.376-15.389; p-value 0.01) compared to non-responders. Ninety-six patients were genotyped for Taq1A DRD2 gene (AA=9, AG=46, GG=41) and found no association (p=0.6) between genetic variants and response to risperidone. ConclusionPatients were showing more than 20% increase in prolactin levels had a better chance of responding to risperidone therapy. Taq1A DRD2 gene did not show any association with prolactin elevation and response to risperidone.

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women.

Prolactin and fMRI response to SKF38393 in the baboon.

Background. This study’s goal was to provide dose–response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose–response curves.Methods. We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m. ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D1-like agonists SKF82958 and SKF38393 or the D2-like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928–9.28 mg/kg, N = 5 animals) or pramipexole (0.00928–0.2 mg/kg, N = 1) was given i.v. during a 40-min blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 min after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED50 (estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain.Results. Prolactin rose 2.4- to 12-fold with anesthesia alone, peaking around 50–90 min after ketamine administration and gradually tapering off but still remaining higher than baseline on isoflurane 3–5 h after ketamine. Baseline prolactin level increased with age. SKF82958 0.1 mg/kg i.v. produced no noticeable change in plasma prolactin concentration. SKF38393 produced a substantial increase in prolactin release that peaked at around 20–30 min and declined to pre-drug levels in about an hour. Pramipexole quickly reduced prolactin levels below baseline, reaching a nadir 2–3 h after infusion. SKF38393 produced clear, dose-responsive BOLD signal changes, and across the four regions, ED50 was estimated at 2.6–8.1 mg/kg.Conclusions. In the baboon, the dopamine D1 receptor agonist SKF38393 produces clear plasma prolactin and phMRI dose–response curves. Variability in age and a modest sample size limit the precision of the conclusions.

Iron Deficiency in Infancy Predicts Altered Serum Prolactin Response 10 Years Later

Serum prolactin may reflect CNS dopaminergic function. Because iron deficiency (ID) alters brain dopamine in rats, serum prolactin levels were previously investigated in infants with varied iron status. High serum prolactin levels correlated with behaviors typical of chronic ID. The objective of this study was to determine the effect of infant iron status on serum prolactin levels after a stressor in early adolescence. One hundred fifty-nine of 191 children enrolled in infancy (chronic ID, n = 46; good iron comparison group, n = 113) had serum prolactin measurements after catheter placement at 11-14 y of age. Serum prolactin levels were compared by sex, pubertal status and infant iron status and the pattern of change over time was compared by infant iron status controlling for pubertal stage and background factors. Males and less mature adolescents had lower serum prolactin concentrations than females and more mature adolescents. Controlling for these factors, the serum prolactin response pattern differed significantly by infant iron status. Serum prolactin declined earlier for the chronic ID group. In conclusion, an altered serum prolactin response pattern was observed 10 y after chronic ID in infancy and may suggest a long-lasting effect of ID on the regulation of prolactin.

Dopamine Antagonist Alters Serum Cortisol and Prolactin Secretion in Lactating Holstein Cows

The role of dopamine in regulating glucocorticoid and prolactin secretion was investigated in lactating Holstein cows by characterizing serum cortisol and prolactin responses to fluphenazine, a dopamine receptor antagonist. Twelve anovulatory cows received an intravenous bolus injection of either saline (n=6) or 0.3mg of fluphenazine/kg of body weight (n=6) in wk 2 postpartum. Blood samples were collected every 30min for 4h before and 4h after saline or fluphenazine injection. Serum progesterone concentration was 0.13±0.1ng/mL and did not differ between groups. No difference in serum cortisol concentrations was detected between groups before treatments. Fluphenazine increased serum cortisol concentrations within 30min after fluphenazine administration (>30ng/mL) and concentrations remained elevated throughout the sampling period. Cortisol remained unchanged in saline-treated cows (<10ng/mL). Prolactin concentrations also increased after fluphenazine administration (103.1±3.1ng/mL), but were unaffected by saline (18±3.1ng/mL). Prolactin concentrations remained elevated throughout the sampling period in fluphenazine-treated cows. Our results indicated that a dopamine antagonist increased cortisol, suggesting that endogenous dopamine, at least in part, regulates cortisol and prolactin secretion. These effects are regulated through dopamine receptors in anovulatory lactating dairy cows during the early postpartum period.

Fenfluramine challenge, self-injurious behavior, and aggression in rhesus monkeys

Self-injurious behavior (SIB) and aggression have been linked to reduced serotonergic (5-HT) functioning in both humans and nonhuman primates. The present study examined serum prolactin and cortisol responses to the 5-HT releasing agent d, l-fenfluramine (FEN) in 24 individually housed rhesus monkeys ( Macaca mulatta), 15 of which carried a veterinary record of self-wounding (SW). Subjects received two doses of FEN, 4 and 2 mg/kg, separated by an interval of at least 2 months. For control purposes, monkeys were given an intramuscular saline injection 1 week prior to each FEN challenge. The relationship between the hormonal responses to FEN, wounding history, the rates of self-directed biting and aggression were determined for each animal based on 100 five-minute observations conducted over a period of 12 months surrounding the challenge procedures. Prolactin and cortisol responses to FEN were unrelated either to wounding history or to rates of self-directed biting. However, there were significant inverse correlations between levels of aggression and the prolactin response to both doses of FEN. The present findings provide no evidence for reduced 5-HT system function in rhesus monkeys with SIB under the present challenge conditions. However, the results are consistent with a previously reported inverse relationship between serotonergic activity and aggression. Moreover, a dose-dependent response to FEN was observed only for prolactin, suggesting that this variable is more appropriate than cortisol as an endpoint for FEN challenge in monkeys.

Neonatal ventral hippocampal damage modifies serum corticosterone and dopamine release responses to acute footshock in adult Sprague-Dawley rats.

Rats with excitotoxic neonatal ventral hippocampal lesions (NVHL) manifest in early adulthood a variety of behavioral and neurochemical abnormalities mimicking those seen in patients with schizophrenia. Some of these aberrations implicate malfunction of the midbrain dopamine systems. We studied NVHL effects on dopamine release in the rat frontal cortex, nucleus accumbens, and striatum during acute stress caused by inescapable continuous footshock (0.45 mA). Serum total corticosterone and prolactin levels were used as peripheral indices of stress. As an indirect index of dopamine release, tissue 3-methoxytyramine levels attained in vivo 10 min after monoamine oxidase inhibition was assayed in rats sacrificed by instantaneous microwave fixation of the brain tissue. Nonshocked NVHL rats showed significantly less nucleus accumbens' 3-methoxytyramine accumulation than their sham counterparts. Frontal cortical 3-methoxytyramine levels rose similarly after 20-min footshock in both groups of rats, but while it normalized after 60-min footshock in the sham rats, it did not decrease in the NVHL rats. Nucleus accumbens' 3-methoxytyramine was significantly elevated after either 20-min or 60-min footshock in both groups, whereas striatal 3-methoxytyramine was significantly elevated in the NVHL rats only. Serum corticosterone showed similar elevations in the sham and NVHL rats, but the patterns differed in that there was no attenuation after 60-min footshock in the latter. The lesion did not affect serum prolactin response. These data indicate that neonatal ventral hippocampal damage enhances and prolongs certain neural and neuroendocrine responses to acute physical stressor(s), and thus may affect adaptation and enhance detrimental effects of stress.

Increased Hypothalamic Dopaminergic Tone Only in Early Parous Women with either Malignant or Benign Breast Tumors

To investigate whether the serum prolactin (PRL) response to a dopamine antagonist was different in nonobese, euthyroid women with malignant or benign breast tumors in comparison with healthy women, considering their age at first full-term pregnancy or their nulliparity. Serum PRL concentrations before and 60, 90, and 120 minutes after oral administration of metoclopramide (10 mg) were studied in 122 nonobese, nonsmoking, euthyroid women: 28 who had invasive breast cancer, stage I or II (group 1), 34 who had benign breast disease (group 2), and 60 who were clinically healthy (group 3). These three main groups were subdivided into early and late parous women (< or = 25 and >25 years, respectively) and nulliparous women, and the menopausal status was also considered. Early parous women with invasive breast cancer (both premenopausal and postmenopausal) and early parous premenopausal women with benign breast disease had significantly higher serum PRL concentrations in response to administration of metoclopramide (P<0.05) and a greater area under the PRL curve (P<0.05) than those observed in early parous healthy women. No other significant differences in the serum PRL response were noted between or within groups. The results of this study suggest the existence of an increased hypothalamic dopaminergic tone in early parous women but not in late parous or nulliparous women with malignant or benign breast tumors in comparison with similar healthy women. This finding may represent an adaptive protective mechanism attempting to prevent persistently increased serum PRL concentrations, a factor that could adversely affect the clinical evolution of the disease.

Oral d-fenfluramine test in treatment-refractory depression : Plasma prolactin response compared in patients with and without suicide attempts and in a healthy reference group

Background: Fenfluramine ( d-FEN) has been used as a serotonin challenge agent to assess central serotonin availability. Blunted serum prolactin (PRL) response to d-FEN has been reported in depressed patients, in suicide-prone patients, and in patients with aggression and personality disorders. We have analyzed suicidality in relation to central serotonergic events by comparing the PRL response to d-FEN in chronically depressed patients with and without suicide attempts and in healthy volunteers. Methods: In 56 inpatients (10 patients with and 46 without suicide attempts) with at least 2 years of treatment-refractory depression (TRD) (DSM-IV) and a reference group of 30 healthy adults, the PRL response after an oral dose of 30 mg d-FEN was followed for 5 h. Results: Controlling for group differences in age, sex, and weight, the PRL response to d-FEN did not differ significantly between the three groups. Far from confirming the hypothesis of a blunted PRL response in depressed patients, our results suggest: (1) that duration and treatment resistance of depression may affect the PRL secretion, and (2) that TRD and major depression may differ in biological relationship to suicidal behavior. Limitations: The findings require corroboration in larger and more closely matched study populations. The fenfluramine concentration was not analyzed in blood. Conclusions: PRL responses to d-FEN challenge did not differ between TRD patients with and without suicidality and the healthy reference group. Chronicity/treatment refractoriness per se may be related to a serotonergic mechanism.

The hormonal response to a d-fenfluramine challenge in trained and sedentary men.

The purpose of the present study was to examine the responsiveness of serotonergic receptors in endurance trained and sedentary men. The serum prolactin and cortisol responses to the oral administration of 30 mg of the serotonin releaser and reuptake inhibitor d-fenfluramine were determined in eight male endurance-trained subjects and seven male sedentary controls. A Friedman's repeated-measures test for both the endurance-trained (P = 0.006) and sedentary (P = 0.018) prolactin results demonstrated a change in the mean prolactin concentration over time, but no difference in prolactin response was observed between the subject groups (P = 0.81). In both subject groups, the serum cortisol concentration remained unchanged. However, the mean serum concentration of cortisol for the endurance-trained subjects at each time point tended to be lower than at the corresponding time point for the sedentary subject group and was significantly lower at 180 min (P = 0.04). The present study suggests that, in contrast to an earlier report of down-regulation of 5-HT1A receptor function in endurance-trained subjects in response to a nonspecific challenge, postsynaptic 5-HT2 function as determined by the d-fenfluramine-evoked alteration in the plasma concentration of prolactin is not altered by endurance training.

Effect of Acute and Chronic Oral Zinc Administration inHyperprolactinemic Patients

The inverse relationship between zinc (Zn++) and prolactin (PRL) was detected in in vitro studies, whereas in vivo results are contradictory. In order to evaluate this controversial subject we studied patients with hyperprolactinemia. Basal serum Zn++ levels and serum PRL response to acute and chronic oral Zn++ administration were evaluated in seven patients with prolactinomas and one with idiopathic hyperprolactinemia. Serum PRL levels did not change after acute oral Zn++ administration (37.5 mg), although Zn++ levels increased from 1.11±0.15 to 2.44±0.39 μg/mL (P<0.05). ZnZn++ administration (47.7 mg daily) during 60 days increased serum Zn++ levels from 1.11 ± 0.15 to 1.59 ± 0.58 μg/mL (p < 0.05) but caused no change in serum PRL levels. The TRH tolerance test (200 μg) was performed before and after 60 days of Zn++ administration, and PRL response to TRH was unchangeable and similar in both tests. We concluded that acute or chronic Zn++ administration does not inhibit PRL secretion in basal condition or by TRH effect in hyperprolactinemic patients.

Risperidone is associated with blunting of D-fenfluramine evoked serotonergic responses in schizophrenia

The high 5-HT affinity of some atypical antipsychotic agents is thought to contribute to their clinical efficacy. We examined central 5-HT responses in two groups of ten schizophrenic patients by measuring serum prolactin and cortisol responses to the neuroendocrine challenge D-fenfluramine. One group of patients with schizophrenia was tested after a 2-week neuroleptic free period. A similar group were tested after a mean of 12 weeks treatment with the atypical antipsychotic risperidone. A significant elevation of baseline serum prolactin levels, consistent with dopaminergic antagonism was seen after risperidone treatment. Significantly reduced 5-HT mediated serum prolactin responses were seen in risperidone treated patients. D-fenfluramine evoked serum prolactin responses were positively correlated with positive but not negative schizophrenic symptoms for all 20 patients. Risperidone treatment was associated with a significant functional in-vivo 5-HT antagonism similar to clozapine. 5-HT antagonism may contribute to the efficacy of risperidone against positive schizophrenic symptoms.

171. Serum cholesterol and impulsive aggressive behavior in personality disorder patients

Background:Decreased serum cholesterolhas beerr associated with impulsive and aggressive behaviors. Abnormal central serotonergic activity,as reflectedby decreasedprolactirrresponsesto fenfluramine, has been correlatedto impulsivityand aggressionin personalitydisordered patients. This study was designedto explore the relationship betweenserumcholesterollevels,serotonergicindicesand measuresof impulsivityand aggressionin personalitydisorderedpatienta.Method: Forty-twopersonalitydisorderedpatients(DSMIHR-20femalesand 22 males,age 37.1+ 8.5),including14patientswithBPD(age:34.2t 6.6; 10female,4 male),and28patientswithotherpersonalitydisorders(age: 38.5t9.l; 10female,18male)wereexaminedforevidenceof irritability and aggressionby self reportas measuredby the Buss-DurkeeHostility Inventory(BDHI),and for evidenceof impulsivityby self report as measuredby the BarratI ImpulsivityScale (BIS).Centralaerotonergic activitywas measuredby the prolactinresponseto fenfluratninechallenge.Fastingserumcholesterolwas measuredby standardenzymatic assay as part of the initial medicalscreening.All patients’thyroidand liverfunctiontests werealso measuredduringinitialmedicrdsermting, and were determinedto be withinnormallimits.Results:An ANOVA wasperformedwithfactorsof genderartddiagnosis,lookingat twoway interactionsbetweenthe factors and serum cholesterol.A significant relationshipwas foundbetweenborderlinediagnosisandreducedsemm cholesterol,(BPDchol=166.8t32.2, non-BPD=192.6*33.6,F= 1.09, p<.05). A significantinteractioneffect was also seen betswxrrgender and diagnosiswith the male patients having lower cholesterollevels (male BPD=154.7 t38.1, non-BPD=203.6t34.3, F=4.33, p<.05). There were no significantrelationshipsbetweenserumcholesteroland scoreson the BIS or the BDHI.There was a trend inversecorrelation between serum cholesterol and prolactin response to fenfluramine (n=18, r.41, p< O.1).Conclusions:This studysuggeststhere may be a relationshipbetweencholesterolandreducedserotonergicactivity.

Serum Prolactin Response to Stressors in Children. • 67

To further describe the relationship between prolactin and behavior in children, sequential serum prolactins were obtained in the course of a follow-up study of iron deficiency in infancy. 167 of the original 191 Costa Rican children (87%) were assessed at 10-13 years of age (mean=12 yr); prolactins were available for 164 subjects. At the time of venipuncture for iron status measures, a catheter was placed indwelling for 4 hours to determine the initial rise and decline of prolactin with venipuncture (0, 15, 30 and 45 min) and prolactin response to a psychological task involving blindfolding, IQ testing, a socially stressful situation and routine dental examination (no fillings). Sera were separated, stored at - 20°C and later assayed by double-antibody RIA for prolactin. Using each child's lowest value as the reference for that child, IQ testing produced trivial changes in serum prolactin. In contrast, serum prolactin rose, on average, 34% after a socially stressful encounter, 62% after a dental exam and 177% after venipuncture. These responses all differed significantly from each other (p<0.1). Males had a greater increase than females after the dental exam (77% vs 39%, p<0.01) but there were no other gender differences. Serum prolactin response to physical or psychological stress has been inconsistently observed in previous studies. Addressing methodologic problems, this study used a larger sample, both genders, varying stressors, and sequential sampling immediately post-stressor. The results show that serum prolactin is a sensitive stress response hormone in children and the degree of the response appears related to the severity of the stressor.

D-fenfluramine-induced prolactin responses in postwithdrawal alcoholics and controls.

Serum prolactin response to the serotonin agonist D-fenfluramine were measured in 19 DSM-111-R male alcoholics, 2.5 or more weeks postalcohol withdrawal. Prolactin responses were compared with nine healthy nonalcoholic male controls. After an overnight fast, each subject received 30 mg of D-fenfluramine orally, and serial samples of serum prolactin were taken over a 4-hr period. D-fenfluramine caused a significantly attenuated peak delta-prolactin response in the alcoholics relative to the controls (p = 0.05). A repeated-measures ANOVA of delta-prolactin yielded a significant within-subjects effect of time (p < 0.05), a within-subjects effect of group that reached significance (p = 0.05), and a nonsignificant group by time interaction. The delta-prolactin value at time points 60 and 240 min postadministration of the probe was significantly attenuated in the alcoholic group, with p < 0.05. There was also some evidence for a diminished serotonergic response in those alcoholics with a negative family history. The delta-prolactin response did not correlate with subjects' age, duration of alcohol use, duration of abstinence from alcohol, severity of alcohol dependence, or age of onset. Results imply a relative subsensitivity of the serotonin system in postwithdrawal alcoholics, and this may be primarily of the 5-HT2 receptor.

Serum prolactin response to ether stress in diabetic rats: opiate system contribution.

Diabetes in streptozotocin-treated rats is associated with alterations in various neuroendocrine systems, including endogenous opioids. These changes are suggested to be responsible for the significant reduction in serum prolactin (PRL) response to a brief restraint stress in diabetic male rats, as compared with normoglycemic controls. The present study examines serum PRL response to ether exposure in diabetic male rats. The animals' response to ether stress, which is known to be related to the opioid system, was examined twice in each rat: shortly after cannula insertion (Day 1), and seven days later. In order to evaluate the opiate system involvement, the experiment was repeated on Day 1 and 7 after surgery in a group of rats which were pretreated with naltrexone (Nalt), an opioid receptor antagonist. Opioid receptor sensitization was also performed by prior acute morphine administration on Day 7 after cannulation surgery. Following adaptation to the cannulation, no difference in serum PRL response to ether stress was found between diabetic and normoglycemic rats. However, on Day 1 after surgery, a significant difference was found between the diabetic and control groups: the normoglycemic (control) group exposed to ether responded to the surgical stress by augmented serum PRL levels. This response was not recorded in the diabetic rats. Opioid receptor blockade by Nalt administration 30 min before ether exposure eliminated this difference. Opioid receptor sensitization by morphine pretreatment facilitated PRL secretion in normoglycemic rats exposed to either, while no effect could be distinguished in the diabetic group. It is therefore concluded that the streptozotocin-induced diabetic rats do not differ from normoglycemic ones in their ability to respond to acute ether stress by itself. However, enhanced PRL secretion induced by ether exposure under additional surgical stress, or by presensitization of the opioid receptors by morphine, is prevented in diabetic rats, probably due to diminished opioid receptor response.

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 microU/ml for women, 500 microU/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 postictal PRL levels. A decrease in PRL response is known to occur if there is progression to status epilepticus.

Serum prolactin response to thyrotropin-releasing hormone during status epilepticus

Determination of serum prolactin can help distinguish between epileptic and pseudo-epileptic attacks since generalized tonic-clonic and complex partial seizures frequently are accompanied by a transient rise in prolactin. In status epilepticus, however, serum prolactin levels are well within the normal range: cellular depletion due to the prolonged seizure activity has been suggested as a mechanism for this finding. The control of prolactin secretion is complex. Among several possible regulators, inhibitory dopamine and stimulatory thyrotropin-releasing hormone (TRH) may take part in the regulation of prolactin levels in connection with epileptic activity. There may be subpopulations of prolactin-producing cells that react differently in response to various regulators. A dopamine receptor blocker given during status epilepticus brings forth a distinct increase in prolactin levels. In order to add to the understanding of prolactin changes in connection with status epilepticus, we injected TRH i.v. during status epilepticus in seven consecutive patients. All patients had prolactin levels within the normal range (< 25 micrograms/l) before injection of TRH which resulted in at least a two-fold increase in prolactin levels. Our results contradict the hypothesis of cellular depletion of prolactin in connection with status epilepticus. The mechanism behind prolactin values within the normal range after prolonged seizure activity remains unknown.