This research communication screened and identified differentiated expressed genes in bovine mammary epithelial cells (BMECs) upon prolactin (PRL) stimulation. PRL of 5 μg/ml increased β-casein synthesis in BMECs with milk protein synthesis capacity. RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs). A total of 375 DEGs (165 up-regulated and 210 down-regulated) were identified between PRL-stimulated group and the control group. Gene ontology enrichment analysis showed that the up-regulated genes were primarily associated with cell functions, metabolic processes, and biological regulatory processes. Pathway enrichment analysis showed that the up-regulated genes were mainly enriched in JAK-STAT, Rap1, Ras and Notch signaling pathways, which are widely involved in cell proliferation, differentiation and milk component synthesis. This study provides an initial understanding of the changes in gene expression in BMECs with PRL-stimulation, as determined by RNA-seq transcriptomic analysis, thereby enhancing our knowledge of the molecular regulation of lactation metabolism.

The effects of food and/or water deprivation at different ambient temperatures (7 or 35 °C) on stress hormone release in sheep (n = 8), were studied to provide background data for research into the effects of road transport. Blood samples were taken from catheterized animals at the start and, at 6h intervals, during 48h tests in an environmental chamber. Cortisol release was unaffected by temperature or deprivation state but was stimulated by introduction to the chamber. Prolactin secretion showed a similar tendency and levels of this hormone were generally higher in the first test, whichever chamber was used. Heat exposure also had a prolonged stimulatory effect on prolactin release, especially in the first test. Growth hormone concentrations were rather variable but tended to be greatest when the animals were deprived of food. Measurements of plasma osmolality indicated that sheep remained in water balance, even when water was withheld for 48h, unless they had access to food. The results suggest that under laboratory conditions, and over a wide thermal range, withholding food and water for 48h does not induce Cortisol or prolactin release in sheep. However, exposure to novel situations seems to have a stimulatory effect.

Advocating for good physical healthcare for their patients is of the utmost importance to psychiatrists. This narrative review focuses on one part of this large goal, the topic of hyperprolactinaemia from the perspective of mental healthcare. For psychiatrists this often includes managing raised prolactin levels in the context of medication. However, they must consider the wider differentials of a raised prolactin level and the possible impact of treatments. For that reason, in this review we start with an overview of prolactin physiology before considering hyperprolactinaemia both in the context of antipsychotic therapy and its wider differentials, including prolactinoma. Investigation and management are considered and key practice points developed.

The thyrotropin (TSH) and prolactin (PRL) responses to protirelin (TRH) were studied in 62 female unipolar depressive patients, 24 delusional (psychotic) and 38 nondelusional (Diagnostic and Statistical Manual [DSM]-III-R criteria). The TSH response to TRH was blunted (≤6 μlU/mL) in ten of the 24 delusional (41.6%) and in 18 of the 38 nondelusional (47.4%) patients, the difference being not significant. The TSH and PRL responses to TRH, calculated as area under the curve, were not different between the two groups. Similar results were obtained when the response patterns were compared by repeated measure analysis of covariance.

Nimodipine was administered at the daily dose of 90 mg po, for 30 days, to ten chronic undifferentiated schizophrenics, eight men and two women, aged 31-35 years, maintained on previously longlasting neuroleptic treatments. In five patients, a placebo period of 15 days preceded the administration of the drug. Monitoring of psychiatric symptomatology by the Brief Psychiatric Rating Scale (BPRS) revealed significant nimodipine-induced improvement. However, the Andreasen Rating Scale for Positive Symptoms (SAPS) showed favourable effects only in the five patients who had not received placebo, while in the others both SAPS and the Andreasen Rating Scale for Negative Symptoms (SANS) showed no significant effect of therapy. The Tardive Dyskinesia Scale revealed no improvements of neurological symptoms after either placebo or drug treatment. Measurement of plasma MHPG concentrations revealed no significant changes induced by either placebo or nimodipine, while HVA plasma levels showed a trend toward decrease, and prolactin a trend toward increase, after nimodipine.

Certain studies on measures related to central neurotransmitter activity have demonstrated that in delusional (psychotic) depression there is a dopaminergic dysregulation which distinguishes it from non-psychotic depression. A neuroendocrinologic method to check the degree of DA receptor responsivity is by measuring the prolactin responses to acute intramuscular administration of haloperidol. We studied this possibility by applying the haloperidol test in seven delusional and ten non-delusional depressed patients. All patients met DSM-IV criteria for a major depressive episode, single or recurrent, with or without psychotic features. After a three-week washout period, 5 mg of haloperidol were injected i.m. and blood samples were taken at 0, 30, 60, 90 and 120 minutes. In both trials, significant time effects were observed (elevated prolactin levels, F = 11.36, P = 0.000). However, the prolactin responses to haloperidol did not differ significantly between the two patient groups (F = 0.12, P = 0.97). These data do not show a difference in D2 receptor responsivity, at least at the hypothalamus-pituitary level, between psychotic and non-psychotic depression.

Six chronic neuroleptic-resistant schizophrenic patients, partial responders to clozapine, were co-administered 600 mg/day of sulpiride (a selective D2 dopaminergic antagonist) as an augmentation to clozapine (a relatively weak D2 blocker), for 10 weeks, open-labeled. A remarkable reduction in positive and negative symptoms was observed in four of the six patients.

The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5–40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5–10 mg/day, mean 9.7) and high (15–40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.

The prolactin (PRL) responses to 5 mg im haloperidol were assessed in the drug-free state and after one month treatment with neuroleptics in 14 male schizophrenic patients who had never received drug treatment, and in 20 male patients who had discontinued their neuroleptic treatment for periods of two months to one year. Drug experienced patients showed lower PRL increases after acute haloperidol (mean 31.7 ng/ml) than drug-naive patients (mean responses 43.4 ng/ml). After treatment with neuroleptics in doses appropriate for the best clinical response, the baseline PRL levels were similar in the two groups, and im haloperidol did not cause any further PRL increases. The results provide evidence that after discontinuation of neuroleptics, the hypothalamic-pituitary dopamine receptors are subsensitive, and remain in that state for long periods of time.

We studied circadian thyrotropin (TSH) and prolactin (PRL) response to synthetic thyrotropin-releasing-hormone (protirelin) infusion (200μg IV) at 8 am and 11 pm in 35 drug-free inpatients with DSM III-R Major Depressive Episode and in 22 hospitalized controls. In each group, maximum TSH and PRL responses were lower at 8 am than at 11 pm. The difference between 11 pm-ΔTSH and 8 am-ΔJTSH (ΔΔTSH) was significantly lower in depressed patients compared to controls. No such blunting was observed in PRL responses to protirelin in depressed patients. In the overall population, TSH response to protirelin (ie8 am-ΔTSH, 11 pm-ΔTSH, ΔΔTSH) correlated significantly with TSH circadian parameters (ie mesor and amplitude). These correlations were also observed with PRL (except for ΔΔPRL). TSH mesor and amplitude were lower in depressives than in controls. In contrast, PRL mesor and amplitude were not significantly different between diagnostic groups. ΔΔTSH is thus a chronobiological refinement to the measure of thyroid axis dysfunction in major depression. The blunted TSH response to protirelin suggests that the TRH receptors of the pituitary thyrotrophs are hyposensitive in major depression.

This Research Communication describes the association between genetic variation within the prolactin (PRL) gene and the milk production traits of Italian Mediterranean river buffalo (Bufala mediterranea Italiana). High resolution melting (HRM) techniques were developed for genotyping 465 buffaloes. The association of genetic polymorphism with milk production traits was performed and subsequently the effects of parity and calving season were evaluated. Single nucleotide polymorphisms (SNPs) were identified at exons 2 and 5 and at introns 1 and 2. All the SNPs were in Hardy–Weinberg equilibrium, and statistical analysis showed that the polymorphism of intron1 was significantly (P < 0·05) associated with milk yield, milk protein content and peak milk yield. The average contribution of the intron1 genotype (r2intron1) to total phenotypic variance in milk production traits was 0·09, and the TT genotype showed lower values than CC and CT genotypes. A nonsynonymous SNP was identified in exon 2, which resulted in an amino acid change from arginine to cysteine. Moreover, the polymorphism of exon 2 was associated significantly with milk fat content (P < 0·05), and the buffaloes with TT genotype showed higher total fat content than the buffaloes with CT genotype. These findings provide evidence that polymorphisms of the buffalo PRL gene are associated with milk production traits and PRL can be used as a candidate gene for marker-assisted selection in Italian Mediterranean river buffalo breeding.

Silymarin is an extract from the plant milk thistle that was shown to have antioxidant and hyperprolactinemic properties. Taking into account the essential role of prolactin for lactating sows and the systemic oxidative stress occurring during lactation, it is of interest to investigate the potential beneficial effects of silymarin on lactating sows. A study was therefore carried out to determine the effects of providing either 1 or 8 g/day of the plant extract silymarin to lactating sows. Sows in first, second or third parity were fed conventional diets during gestation and, at farrowing, were assigned as controls (CTL, n=33), or were fed 1 g/day (SYL1, n=33) or 8 g/day (SYL8, n=33) of silymarin. The silymarin was provided in two equal amounts per day, and was fed throughout a 20-day lactation. The performance of sows and their litters was assessed and circulating concentrations of prolactin (days 7 and 18), urea (days 7 and 18) and oxidative status, via protein carbonyls and superoxide dismutase activity (day 18), were measured in sows. Milk samples were obtained on day 18 to measure standard composition. There was no effect of silymarin (P>0.10) on circulating prolactin or urea, or on oxidative damage to proteins or antioxidant potential in sows. Lactation feed intake, backfat and BW of sows were unaffected by treatment (P>0.10) as was the case for milk composition and piglet growth (P>0.10). Results demonstrate that providing up to 8 g/day of the plant extract silymarin to lactating sows had no beneficial effects in terms of circulating prolactin concentrations or oxidative status of sows, or in terms of performances of sows and their litters.

Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to increase the risk of erectile and ejaculatory disorders in male patients and to menstrual disturbances in female patients. In the literature reviewed, risperidone is associated with higher prolactin levels in comparison to classical antipsychotics. It is still unclear which mechanism is responsible for the increase of serum prolactin levels and sexual dysfunctions in patients using risperidone. Dopaminergic and serotonergic receptor blockade seems to play an important role. Other mechanisms are discussed.

The length of the dry period in commercial dairy production is under close scrutiny. While the main concern is the composition and volume of milk produced, the evaluation of colostrum quality under these new paradigms has suggested a decline in IgG concentrations, while some reports indicate no change. Colostrum quality has been defined as an adequate concentration (>50 mg/ml) of immunoglobulin in the secretions to provide the newborn with maximal disease resistance. We investigated the appearance of IgG in mammary pre- and post partum secretions in cows without a dry period (continuously milked, Dry0) and compared the secretions with cows that experienced a dry period of 60 d (Dry60). Blood was collected during the experimental period and plasma analysed for progesterone (P4) and prolactin (Prl). Approximately −6 d relative to parturition, the Dry0 animals exhibited increased concentration of IgG in their secretions to an average of ∼35 mg/ml that remained rather constant through subsequent pregnancy and following parturition. Dry0 cows were producing an average IgG concentration in parturition colostrum of 44·2±17·6 mg/ml that was not different than that of controls (66·86±16·8 mg/ml). However, Dry0 cows exhibited high variation, different peak times (day) of IgG concentration including times that occurred both pre and post parturition. IgG mass of the Dry0 cows remained rather constant pre- and post partum and did not show the same declining mass following parturition that was shown for the Dry60 cows. The change in plasma P4 and Prl were shown to have no timing effect on colostrum IgG concentration.