Changes In Prolactin Research Articles

Short-term effects of alcohol consumption on the hormonal milieu and mood states in nulliparous women

The present study was designed to determine the short-term effects of alcohol consumption on hormonal responses and mood states in nulliparous women who have regular menstrual cycles. To this aim, we conducted a within-subjects design study in which eight women consumed a 0.4-g/kg dose of alcohol in orange juice during one test session (alcohol condition) and an equal volume of orange juice (control condition) during the other. Changes in plasma prolactin, oxytocin and cortisol levels, blood alcohol concentrations (BACs), and mood states were compared. BAC peaked at approximately 36.7 + 5.4 min after the consumption of the alcoholic beverage and decreased thereafter. Alcohol consumption significantly increased the area under the concentration–time curve (AUC) of prolactin ( P < .01) and decreased the oxytocin AUC ( P = .04) when compared to the control condition. Cortisol AUCs were not different across the two experimental conditions. Similar to that previously observed in lactating women, changes in prolactin and oxytocin paralleled changes in feelings of drunkenness. The magnitude and persistence of the alcohol-induced hormonal changes in nulliparous women were significantly less pronounced than those observed in lactating women, further highlighting the dynamics of the system under study during lactation.

Neuroendocrine modulation of stress response in the anuran, Rana esculenta

AbstractIn amphibians, as in other vertebrates, stress stimuli have been found to affect different functions, including development, growth, and reproduction. A wide range of responsiveness to stressors has been reported for amphibians; for instance, capture and/or captivity stress induced changes both in the hypothalamus-pituitary-interrenal and hypothalamus-pituitary-gonadal axes. However, few studies have examined the response to stress in terms of recovery and/or adaptation by applying stress paradigms for a short and long-term duration. In the present paper, the short-term captivity stress responses were evaluated in the anuran Rana esculenta by measuring peripheral corticosterone, androgens, prolactin (PRL), and growth hormone (GH) changes. Moreover, in long-term captivity and salinity stress, effects were evaluated by measuring peripheral PRL changes and those of PRL mRNA in the pituitary together with plasma corticosterone and androgens. Short-term (24 h) captivity stress induced an increase of peripheral corticosterone together with that of GH and PRL since these hormones are involved in the "alarm phase" and in energy demand of stressed animals. The opposite trend was found for peripheral androgens, in view of the negative effects exerted by stress in the reproductive axis. In long-term (1 month) captivity and salinity stress, responses were consistent with the increasing of PRL mRNA at pituitary level, through a long-loop feedback mechanism depending on the decreasing levels of peripheral PRL, whereas no changes were found in the levels of plasma corticosterone and androgens. Therefore, it seems that Rana esculenta activates different neuroendocrine mechanisms depending on the duration of stress and on the types of stressors.

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6–8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Coding for the Initiation of Pseudopregnancy by Temporally Patterned Activation of Amygdalar NMDA Receptors

Female rats modulate the number and interval between the intromissions the female receives during mating. This patterned vaginocervical stimulation (VCS) is critical for triggering long-term changes in prolactin (PRL) secretion necessary for pregnancy or pseudopregnancy (P/PSP). Previous work has shown that NMDA receptor activation in the posterodorsal medial amygdala (MEApd) is required at the time of mating for VCS to induce the twice-daily PRL surges characteristic of P/PSP. The current studies examined whether patterned activation of glutamate receptors within the MEApd induces P/PSP. In anesthetized, cycling females, three 0.27 microg NMDA infusions given at 30 min intervals into the MEApd initiated P/PSP, whereas a single NMDA infusion of the same total dose (0.8 microg) had no effect. In conscious, freely behaving females, three infusions of an excitatory amino acid (EAA) mixture applied at the same interval were more effective in initiating P/PSP and nocturnal PRL surges than were single infusions at the same or higher concentrations. Infusion intervals of 5 and 60 min as well as continuous 1 h infusion did not induce P/PSP. Finally, a synergistic effect was observed between EAA and mating stimulation, because a subthreshold EAA infusion combined with subthreshold numbers of intromissions induced P/PSP. These results demonstrate that repeated, properly spaced, temporally discreet periods of glutamate receptor activation within the MEApd, which mimic mating stimulation, encode for P/PSP. Such findings suggest that single intromissions normally release individually subthreshold quanta of glutamate within the MEApd that summate to induce P/PSP.

Double-Blind, Placebo-Controlled Investigation of Amantadine for Weight Loss in Subjects Who Gained Weight With Olanzapine

This study sought to determine if amantadine affects weight gain in psychiatric patients taking olanzapine. Twenty-one adults who had gained at least 5 lb with olanzapine were randomly assigned to receive amantadine (N=12) or placebo (N=9) in addition to olanzapine. The length of time taking olanzapine ranged from 1 to 44 months. Body mass index, psychiatric status, and fasting blood levels were assessed at baseline and 12 weeks. Significantly fewer subjects taking amantadine gained weight, with a mean change in body mass index of -0.07 kg/m2 for the amantadine group and 1.24 kg/m2 for the placebo group. This effect remained significant when the authors controlled for baseline body mass index and length of olanzapine treatment. No changes in fasting glucose, insulin, leptin, prolactin, and lipid levels were seen. Positive and Negative Syndrome Scale scores remained stable. Amantadine induced weight stabilization in subjects taking olanzapine and was well tolerated.

CRH receptor type 1 mediates continual hypoxia-induced changes of immunoreactive prolactin and prolactin mRNA expression in rat pituitary

We have reported that, in rats, hypoxia (10.8% O 2) stimulates prolactin (PRL) release from the pituitary. This study is designed to compare the response of pituitary PRL to acute hypoxia (AH), continual hypoxia (CH), intermittent hypoxia (IH), cold, and restraint, individually and combined with hypoxia. This study also investigates the involvement of the corticotropin-releasing hormone receptor 1 (CRH R1) in the hypoxia-induced PRL response. Hypoxia was induced by exposing the rats to high altitudes of 2 km (16.0% O 2) or 5 km (10.8% O 2). The PRL levels in the pituitary (iPRL) and in plasma (pPRL) were measured by immunocytochemistry and RIA assay, respectively. The acute hypoxia of 5 km for 2–24 h caused a biphasic change (early decrease and late increase) of PRL. Both CH and IH at 2 or 5 km for 1–5 days markedly increased pPRL but decreased iPRL. Continual severe hypoxia (10.8% O 2) for periods of 10, 15, and 25 days significantly enhanced pPRL but this effect was less marked at the lower altitude (16.0% O 2) and did not occur during intermittent hypoxia (at both altitudes). The increased pPRL was significantly enhanced by restraint, restraint + hypoxia, hypoxia, and cold + hypoxia exposure. Treatment with a CRH R1 antagonist (CP-154,526) reversed hypoxia-decreased immunoreactive PRL and upregulated PRLmRNA in the pituitary. The data suggest that both CH and IH can stimulate rat PRL release in a time-course- and intensity-dependent manner. However, compared to the relatively low CH-induced response, restraint induced a more powerful response than either cold or hypoxia alone. CRH R1 mediates PRL secretion and PRL mRNA expression in the pituitary under hypoxic exposure. Hypoxia-enhanced PRL response over the lifespan may play a significant role in adaptation to an extreme environment.

The post-orgasmic prolactin increase following intercourse is greater than following masturbation and suggests greater satiety

Research indicates that prolactin increases following orgasm are involved in a feedback loop that serves to decrease arousal through inhibitory central dopaminergic and probably peripheral processes. The magnitude of post-orgasmic prolactin increase is thus a neurohormonal index of sexual satiety. Using data from three studies of men and women engaging in masturbation or penile–vaginal intercourse to orgasm in the laboratory, we report that for both sexes (adjusted for prolactin changes in a non-sexual control condition), the magnitude of prolactin increase following intercourse is 400% greater than that following masturbation. The results are interpreted as an indication of intercourse being more physiologically satisfying than masturbation, and discussed in light of prior research reporting greater physiological and psychological benefits associated with coitus than with any other sexual activities.

Circadian variations in plasma concentrations of melatonin and prolactin during breeding and non-breeding seasons in yak ( Poephagus grunniens L.)

Circadian variations of plasma melatonin and prolactin concentrations were determined during breeding as well as non-breeding seasons in yak. Blood samples (5 ml) were collected during different phases of estrous cycle, viz. early (0–6 days), mid (7–12 days) and late luteal (13–19 days) at 2 h interval for 24 h from eight yaks during one breeding month (November); the same yaks were bled at 2 h interval during one non-breeding month (February) for 24 h. Plasma melatonin concentrations rose sharply ( P < 0.01) after sunset to record peak concentrations between midnight and 2 a.m. declining sharply thereafter in both breeding as well as non-breeding seasons. Basal melatonin concentrations were recorded between 0600 and 1600 h. Stage of luteal phase did not influence the diurnal hormone change ( P < 0.01). In the breeding season, mean plasma prolactin concentrations displayed circadian variations with maximum value at 0400 h (41.22 ± 1.5 ng/ml) and minimum at 1400 h (12.0 ± 4.02 ng/ml). In the non-breeding season plasma prolactin concentrations showed circadian variation with maximum value at 0000 h (59.9 ± 10.5 ng/ml) and minimum at 1200 h (32.13 ± 3.2 ng/ml). A positive correlation in breeding ( r = 0.75) and in non-breeding season ( r = 0.65) between circadian changes in mean plasma prolactin and melatonin concentrations were seen. Circadian changes of mean plasma melatonin concentrations during breeding and non-breeding seasons were not different ( P > 0.05). However, mean plasma prolactin concentrations were found to be higher ( P < 0.01) in the non-breeding season. Three conclusions were drawn from the study: (i) melatonin and prolactin concentrations followed a circadian pattern of secretion (ii) melatonin and prolactin secretion may be closely interrelated and (iii) higher prolactin concentrations during the non-breeding season could be due to nutritional and environmental stress and hence might be contributing to lack of cyclicity.

Differences in reproductive pattern between wild and domestic rams are not associated with inter-specific annual variations in plasma prolactin and melatonin concentrations

This study compares morphological changes, performed with real-time transrectal ultrasonography, of testis and accessory glands and seasonal endocrine changes in a wild (Mouflon) and a domesticated (Spanish Merino) breed of sheep. In Mouflons, the maximum plasma testosterone concentrations, testicular diameter and vesicular gland size occurred synchronously during autumn ( P < 0.001). In Merino rams the highest circulating levels of testosterone ( P < 0.05) and maximum testicular diameter ( P < 0.001) occurred during summer, with no seasonal variations in vesicular and bulbourethral glands. The seasonal changes in plasma concentrations of prolactin were not correlated with annual variations in testicular and glandular size in neither wild nor domestic species. No differences were observed between both species for the seasonal pattern of prolactin secretion and mean amplitude of melatonin. Wide differences in reproductive patterns between wild and domestic types of rams do not appear to be attributed to seasonal changes in prolactin and melatonin secretion.

Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the hypothalamic–pituitary–adrenal axis and inhibition of prolactin secretion

Immune activation results in adaptive neuroendocrine responses, including activation of the hypothalamic-pituitary-adrenal axis, which are dependent on the integrity of medullary catecholaminergic (CA) systems. In contrast, although specific roles of pontine, midbrain, and hypothalamic CA systems in neuroendocrine function have been described, the functional roles of these CA systems in modulating neuroendocrine function during immune responses have not been investigated. We have, therefore, investigated the effects of immune activation on the various CA systems of the central nervous system (CNS) and explored this relationship with changes in plasma corticosterone and plasma prolactin. Male BALB/c mice were injected with lipopolysaccharide (LPS, 500 microg/kg i.p.) and 2 h later cardiac blood was taken and mice were perfused with fixative. Immunostaining procedures were performed using antibodies raised against c-Fos and tyrosine hydroxylase, a marker of CA neurons, and detailed topographical analysis of the CA systems within the CNS was performed. LPS-injected mice had increased concentrations of plasma corticosterone and decreased concentrations of plasma prolactin compared with vehicle-injected controls. LPS-injected mice had increased numbers of c-Fos-positive CA neurons within the medullary (A1, A2, C1, C2), pontine (A6) and midbrain (A10) cell groups when compared with vehicle-injected controls. Among hypothalamic CA cell groups, LPS had differential effects on the numbers of c-Fos-positive CA neurons in topographically organised subdivisions of the arcuate nucleus (A12). Changes in plasma prolactin concentrations correlated with the numbers of c-Fos-positive CA neurons within the area postrema, the medullary CA cell groups, the medial posterior division of the arcuate, and the zona incerta. The present study identifies topographically organised, anatomically distinct CA systems that are likely to modulate some of the neuroendocrine responses to immune activation, and may provide novel targets for the relief of symptoms associated with illness and disease.

Urinary prolactin is correlated with mothering and allo-mothering in squirrel monkeys

The hormone prolactin is implicated in infant care-giving by parents and allo-parents in a variety of species. Adult female squirrel monkeys ( Saimiri spp.) engage in allo-mothering behavior, which includes carrying and nursing infants, but communal care of offspring has not been investigated from an endocrine standpoint in this taxon. We attempted to fill this gap by examining prolactin levels in squirrel monkeys ( Saimiri sciureus) as a function of parental responsiveness. Subjects were housed at the National Institutes of Health Animal Center and assays were performed at the Wisconsin National Primate Research Center. To test for the presence of prolactin in squirrel monkey, saliva, blood and saliva were simultaneously collected from anesthetized subjects during routine health examinations. Prolactin was detectable in serum but not in saliva samples. In the core investigation, behavioral data were collected by focal animal sampling on three 1-male multi-female groups, and individually identified urine was collected non-invasively from foil containers underneath group cages on a daily basis throughout the behavioral study. Changes in urinary prolactin over time reflected changes in the reproductive state of a female who was pregnant, gave birth and lactated during the study. Mean urinary prolactin levels in non-lactating females and a male housed with infants in one group were higher than in adults from 2 groups without infants. In the group with infants, mean urinary prolactin levels in adults increased with the amount of infant contact and care-giving. The squirrel monkey may represent a new primate model for investigating the endocrinology of infant care-giving.

Acute alcohol consumption disrupts the hormonal milieu of lactating women.

Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advised to drink alcohol as an aid to lactation for centuries. To test the hypothesis that alcohol consumption affects the hormonal response in lactating women, we conducted a within-subjects design study in which 17 women consumed a 0.4 g/kg dose of alcohol in orange juice during one test session and an equal volume of orange juice during the other. Changes in plasma prolactin, oxytocin, and cortisol levels during and after breast stimulation, lactational performance, and mood states were compared under the two experimental conditions. Oxytocin levels significantly decreased, whereas prolactin levels and measures of sedation, dysphoria, and drunkenness significantly increased, during the immediate hours after alcohol consumption. Changes in oxytocin were related to measures of lactational performance such as milk yield and ejection latencies, whereas changes in prolactin were related to self-reported measures of drunkenness. Although alcohol consumption resulted in significantly higher cortisol when compared with the control condition, cortisol levels were not significantly correlated with any of the indices of lactational performance or self-reported drug effects. Moreover, cortisol levels steadily decreased on the control day, indicating that the procedures were not stressful to the subjects. In conclusion, recommending alcohol as an aid to lactation may be counterproductive. In the short term, mothers may be more relaxed, but the hormonal milieu underlying lactational performance is disrupted, and, in turn, the infant's milk supply is diminished.

Plasma prolactin changes in anoestrous ewes after infusion of genistein into the third ventricle

Plasma prolactin changes in anoestrous ewes after infusion of genistein into the third ventricle

Influence of age on the relationship between annual changes in horn growth rate and prolactin secretion in the European mouflon ( Ovis gmelini musimon)

Annual variations in the growth of horns, and their correlation with seasonal changes of testicular size, and prolactin (PRL) and melatonin secretion were monitored in six pubertal mouflon rams living in their original latitude (40°N). Mouflons born and maintained under captive conditions were classified in two age classes: sub-adult (2 years; n = 3) and adult (≥3 years; n = 3). The rate of horn growth was greater ( P < 0.001) in sub-adult than in adult mouflon rams. Horn growth was influenced by season in both adult and sub-adult mouflons ( P < 0.05) with largest monthly growth occurring in spring and summer. Seasonal variations of plasma PRL concentrations were correlated with horn growth in adult, but not in sub-adult mouflon rams. The rate of horn growth was inversely correlated with testicular size ( r = −0.5, P = 0.07). Seasonal changes in the amplitude of the daily melatonin rhythm in solstices and equinoxes were observed, which were not correlated with variations in the rate of horn growth. These results provide support for a possible role of PRL in the control of growth of horns in the adult mouflon.

Pivotal role of an endogenous tetrahydroisoquinoline, salsolinol, in stress- and suckling-induced release of prolactin.

In mammals, the role of a prolactin-releasing factor (PRF) in the acute changes of prolactin (PRL) secretion that usually occur after challenges (e.g., suckling stimulus or stress) of homeostasis has been suspected for a long time. We have recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, salsolinol (SAL), produced by the hypothalamus and the neuro-intermediate lobe (NIL) of the pituitary gland, can selectively release PRL from the anterior lobe (AL). Moreover, binding sites for SAL have been detected in areas like median eminence, NIL, and AL. It has been proposed that SAL is a putative endogenous PRF. We have also found that a structural analogue of SAL, 1-methyl-3,4-dihydroisoquinoline (1MeDIQ), is able to block dose-dependently SAL-, suckling-, and immobilization (IMO) stress-induced release of PRL without having any influence on alpha-methyl-p-tyrosine (alphaMpT)-induced PRL responses. Neither SAL nor 1MeDIQ has any effect on alpha-melanocyte-stimulating hormone (alphaMSH), adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END) and arginine-vasopressin (AVP) secretion. Moreover, SAL-induced PRL response was attenuated in male rats pretreated with dexamethasone (DEX). These results strongly suggest that SAL has an important role in the regulation of PRL release induced by physiologic and environmental stimuli; therefore, it can be considered as the strongest candidate for being the PRF in the hypothalamo-hypophysial system. Our findings also indicate that the adrenal steroids may play an inhibitory feedback role in SAL-mediated PRL response.

Effect of Lirukang oral liquid on neurotransmitters and estrogen in rats with hyperplasia of mammary gland

Objective: To investigate the effects of Lirukang oral liquid (LRK) on release of neurotransmitter in rats with hyperplasia of mammary glands (HMG) and to explore its mechanism.Methods: Sixty rats were divided into six groups, the normal control group, the model control group, the large dosage (3.6g/kg) and the small dosage (1.8g/kg) LRK groups, the Ruzengning (RZN, 2.5g/kg) group and the tamoxifen (TAM, 5mg/kg) group, 10 in each group. Except those in the normal control group, all the animals were made into rat model of HMG by intraperitoneal injection of estradiol benzoate. Levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in hypothalamus and mammary gland in rats were detected by fluorescence luminosity assay, and level of prolactin (PRL) in serum was detected by radioimmunoassay.Results: In the model group, the level of DA reduced significantly (P<0.01), and 5-HT and PRL increased obviously (P<0.01). Compared with the model group, the LRK groups of both dosages and the TAM group had their level of DA significantly increased (P<0.01), and level of 5-HT significantly decreased (P<0.01). The serum PRL in both LRK groups was significantly decreased (P<0.01). No obvious changes in DA, 5-HT and PRL were found in the RZN group.Conclusion: LRK and TAM have similar effects in regulating the release of neurotransmitter in hypothalamus and mammary gland and serum content of estrogen in the animal models of HMG.

Temporal association between serum prolactin concentration and exposure to styrene

Background: Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL). Aims: To test the hypotheses that: (1)...

Genistein, a Phytoestrogen, Effectively Modulates Luteinizing Hormone and Prolactin Secretion in Ovariectomized Ewes during Seasonal Anestrus

Through binding with estrogen receptors, phytoestrogens, plant-derived estrogen-like compounds, affect numerous reproductive functions. It is not known whether these compounds are capable of evoking effective changes in luteinizing hormone (LH) and prolactin (PRL) secretion in ewes by acting directly within the central nervous system (CNS). The hypothesis studied was that genistein, infused for several hours into the third ventricle, could immediately affect LH and PRL secretion in ovariectomized (OVX) ewes during seasonal anestrus. Two doses of genistein, 1 µg/100 µl/h (total 4 µg, n = 7) and 10 µg/100 µl/h (total 40 µg, n = 7), were infused intracerebroventricularly from 12.00 to 16.00 h and blood samples were collected from 8.00 to 20.00 h at 10-min intervals. Randomly selected ewes were infused with a vehicle (control, n = 5). The mean plasma LH concentration in control ewes was significantly (p < 0.01) higher during infusion of the vehicle than before the infusion. It remained on an insignificantly changed level after the infusion. The frequency of LH pulses in control ewes did not differ significantly before, during, or after vehicle infusion. In ewes infused with a lower dose of genistein, plasma LH concentrations decreased significantly (p < 0.001) after the infusion, as compared with the values noted before and during genistein infusion. Only a tendency towards a decrease in LH pulse frequency occurred after infusion of a lower dose of genistein. In ewes infused with a higher dose of genistein, the plasma LH concentration decreased significantly (p < 0.01) after phytoestrogen administration as compared with the values noted before and during infusion. The frequency of LH pulses was also significantly (p < 0.01) lower after genistein administration. Because the changes in PRL secretion were more dynamic in response to genistein infusion, the statistical analysis included 2-hour periods. The mean plasma PRL concentration in control animals was significantly enhanced (p < 0.01) only during the first 2-hour period of sampling. After that it decreased and remained on an unchanged level up to the end of sampling. Similar changes in PRL secretion were observed in both experimental groups before genistein infusion. In contrast, significant (p < 0.01 to p < 0.001) increases in PRL concentration were noted regularly during and shortly after the genistein infusion in either low-dose or high-dose genistein-infused ewes, compared with the concentrations noted before genistein treatment. Plasma PRL concentrations during and after genistein infusion in both experimental groups were also significantly higher than the control (p < 0.01 to p < 0.001). The presented data demonstrate that genistein, a phytoestrogen, may effectively modulate LH and PRL secretion in OVX ewes by acting within the CNS.

Responsiveness of expectant male cotton-top tamarins, Saguinus oedipus, to mate's pregnancy

In the cotton-top tamarin, a primate where paternal care is critical to the survival of the offspring, we found that expectant fathers experienced multiple hormonal changes during their mate's pregnancy. Fathers that had experienced several previous births showed significant changes in urinary estrogens, androgens, prolactin and cortisol in the last 2 months before birth, whereas less-experienced fathers (LEF) did not. The female's midpregnancy rise in glucocorticoids was followed within 1–2 weeks by a peak of cortisol and corticosterone in her paired male in 70% of all males and 100% of all experienced males. Examination of behavioral interactions between the pairs did not reveal changes in rates of interactions between the experienced pairs over pregnancy. However, the less-experienced pairs had significantly higher levels of affiliative and sexual interactions. Therefore, behavioral communication between the pair did not appear to account for the hormonal changes occurring within the experienced fathers (EF). The midpregnancy rise of glucocorticoids in females may stimulate a glucocorticoid response in male tamarins and thereby activate other hormonal changes in males to prepare them for their parenting role.

Prolactin levels in risperidone treatment of first-episode schizophrenia

OBJECTS: To evaluate the risperidone effect on prolactin (PRL) levels and to analyse the relation between PRL change and treatment response in first-episode schizophrenia patients.METHOD: Patients with a first-episode of schizophrenia who were consecutively admitted for hospitalisation participated in a longitudinal follow-up study that included clinical evaluation (PANSS) and PRL assessment. All patients were treated under open conditions with risperidone.RESULTS: Risperidone in an average dose lower than 4 mg significantly improved both positive and negative symptoms. Co-operating responders undergoing maintenance therapy showed a mild trend towards further long-term improvement. At the end of acute treatment the average elevation of PRL levels almost doubled the baseline value. There was a trend among responders to return to their initial values during long-term therapy. Three-quarters of the subjects had hyperprolactinaemia at the end of acute treatment (44 days), and after 1 year about one-quarter had hyperprolactinaemia. No significant correlation between PRL change and PANSS score change was found.CONCLUSION: There is a considerable variation of PRL elevation among subjects. In some patients the development of tolerance of the PRL-elevating effect was observed. Risperidone-induced changes of PRL levels may not be associated with treatment response.