Increased Prolactin Concentrations Research Articles

Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene.

Prolactin (PRL) has been reported to influence reproductive performance and cell apoptosis. However, its mechanism remains unclear. Hence, in the present study, ovine ovarian granulosa cells (GCs) were used as a cell model to investigate the relationship between PRL concentration and GC apoptosis, as well as its possible mechanisms. We examined the relationship between serum PRL concentration and follicle counts in sexually mature ewes. GCs were isolated from adult ewes and treated with different concentrations of PRL, while 500 ng/mL PRL was selected as the high concentration of prolactin (HPC). Then, we applied the transcriptome sequencing (RNA-Seq) combined with a gene editing approach to explore the HPC contributing to cell apoptosis and steroid hormones. The apoptosis of GCs gradually increased at PRL concentrations above 20 ng/mL, while 500 ng/mL PRL significantly decreased the secretion of steroid hormones and the expression of L-PRLR and S-PRLR. The results indicated that PRL regulates GC development and steroid hormones mainly through the target gene MAPK12. The expression of MAPK12 was increased after knocked-down L-PRLR and S-PRLR, while it decreased after overexpressed L-PRLR and S-PRLR. Cell apoptosis was inhibited and the secretion of steroid hormones increased after interfering with MAPK12, while the overexpression of MAPK12 showed the opposite trend. Overall, the number of follicles gradually decreased with increasing PRL concentration. HPCs promoted apoptosis and inhibited steroid hormone secretion in GCs by upregulating MAPK12 through reducing L-PRLR and S-PRLR.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Patients with Schizophrenia: A Randomized Controlled Trial

Most antipsychotic drugs are dopamine receptor antagonists that usually lead to abnormal increases in prolactin concentrations and the development of hyperprolactinemia (HPRL), which in turn causes sexual dysfunction in patients. Peony-Glycyrrhiza Decoction (PGD) enhanced dopamine D2 receptors (DRD2) and dopamine transporter (DAT) and significantly reversed the expression of DRD2 and DAT. Therefore, we hypothesized that PGD might effectively improve hyperprolactinemia and alleviate sexual dysfunction in patients. We performed an 8-week randomized controlled study on 62 subjects with schizophrenia who were randomized into two groups. The experimental group was treated with the PGD intervention, and the control group did not receive treatment. The primary outcome indicators were the levels of sex hormones and the total Arizona Sexual Experience Scale (ASEX) score. There was a significant difference in PRL levels between the two groups at weeks 4 and 8. From the beginning to the end of the experiment, there was a significant increase in PRL levels in the control group, while there was no significant change in the experimental group. The ASEX scale assessed sexual function in both groups, and patients in the experimental group showed an improvement in sexual function at week 8. During the experiment, the two groups found no differences between Positive and Negative Syndrome Scale (PANSS) scores and Treatment Emergent Symptom Scale (TESS) scores. PGD significantly improved the patient's sexual function but was less effective in reducing prolactin levels and may prevent further increases in prolactin levels.

Oral administration of domperidone in the first or third week of lactation: Effects on prolactin concentrations and mammary gene expression in sows and piglet growth

The scope of the present study is endocrine and metabolic control of sow lactation. This project aimed to determine the impact of increasing prolactin concentrations via oral administration of the dopamine receptor antagonist domperidone in the first or third week of lactation in sows. Effects on sow hormonal and metabolic status, lactational performance, and gene expression in mammary epithelial cells were determined. Primiparous sows were divided in 3 treatments: 1) 10 mL of vehicle (table syrup) per os twice daily during the first and third weeks of lactation (Control, CTL, n = 23), 2) 0.5 mg/kg of domperidone per os twice daily during the first week of lactation (LACT1, n = 23), or 3) 0.5 mg/kg of domperidone given per os twice daily during the third week of lactation (LACT3, n = 22). Treated sows also received 10 mL of the vehicle twice daily during the other treatment period. Litter size was standardized to 12 ± 1 and piglets were weighed at birth, 24 h, and on d 8, 15, 22 (weaning), 35, and 56. Sow feed intake was recorded daily. Representative milk samples were obtained on d 7 and 21 of lactation for compositional analyses, and milk fat globules were used to measure mRNA abundances of various genes. Jugular blood samples were obtained from sows on d 1, 7, 14, and 21 of lactation to measure concentrations of prolactin, IGF-1, insulin, urea, and FFA. Concentrations of prolactin were increased (P < 0.01) at the end of the 7-d treatment period with domperidone, whether imposed in the first (LACT1) or third (LACT 3) week of lactation. No other blood variables were affected by treatments and neither was milk composition (P > 0.10). Sow BW, backfat thickness, or feed intake were not altered by treatments (P > 0.10), but piglet BW tended to be greater in litters from LACT3 compared with CTL sows on d 22 and 35 (P ≤ 0.10). Gene expression of EGF in milk fat globules tended to be (LACT1, P < 0.10) or was increased (LACT3, P < 0.05) after treatment, and the effect in LACT1 sows was maintained until d 21 of lactation. The mRNA abundance of SPP1 was increased (P < 0.05) in LACT1 vs CTL sows on d 7, and that of 3 major milk proteins tended to be (CSN1S2 and WAP, P < 0.10) or was greater (LALBA, P < 0.05) in LACT3 vs CTL sows on d 21 of lactation. Oral administration of domperidone during the first or third week of lactation increased prolactin concentrations and altered mRNA abundances of selected genes in milk fat globules. Yet, only the LACT 3 treatment positively affected piglet performance.

Predicting psychotic relapse following randomised discontinuation of paliperidone in individuals with schizophrenia or schizoaffective disorder: an individual participant data analysis

Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment discontinuation, using machine learning. For this individual participant data analysis, we searched the Yale University Open Data Access Project's database for placebo-controlled, randomised antipsychotic discontinuation trials with participants with schizophrenia or schizoaffective disorder (aged ≥18 years). We included studies in which participants were treated with any antipsychotic study drug and randomly assigned to continue the same antipsychotic drug or to discontinue it and receive placebo. We assessed 36 prespecified baseline variables at randomisation to predict time to relapse, using univariate and multivariate proportional hazard regression models (including multivariate treatment group by variable interactions) with machine learning to categorise the variables as general prognostic factors of relapse, specific predictors of relapse, or both. We identified 414 trials, of which five trials with 700 participants (304 [43%] women and 396 [57%] men) were eligible for the continuation group and 692 participants (292 [42%] women and 400 [58%] men) were eligible for the discontinuation group (median age 37 [IQR 28-47] years for continuation group and 38 [28-47] years for discontinuation group). Out of the 36 baseline variables, general prognostic factors of increased risk of relapse for all participants were drug-positive urine; paranoid, disorganised, and undifferentiated types of schizophrenia (lower risk for schizoaffective disorder); psychiatric and neurological adverse events; higher severity of akathisia (ie, difficulty or inability to sit still); antipsychotic discontinuation; lower social performance; younger age; lower glomerular filtration rate; benzodiazepine comedication (lower risk for anti-epileptic comedication). Out of the 36 baseline variables, predictors of increased risk specifically after antipsychotic discontinuation were increased prolactin concentration, higher number of hospitalisations, and smoking. Both prognostic factors and predictors with increased risk after discontinuation were oral antipsychotic treatment (lower risk for long-acting injectables), higher last dosage of the antipsychotic study drug, shorter duration of antipsychotic treatment, and higher score on the Clinical Global Impression (CGI) severity scale The predictive performance (concordance index) for participants who were not used to train the model was 0·707 (chance level is 0·5). Routinely available general prognostic factors of psychotic relapse and predictors specific for treatment discontinuation could be used to support personalised treatment. Abrupt discontinuation of higher dosages of oral antipsychotics, especially for individuals with recurring hospitalisations, higher scores on the CGI severity scale, and increased prolactin concentrations, should be avoided to reduce the risk of relapse. German Research Foundation and Berlin Institute of Health.

A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge Regarding Management and Prevention of Breast Engorgement among primigravida Mothers in Selected Hospitals at Rohtas District

Breast engorgement is common among postnatal mothers especially in primigravida mothers. Breast engorgement is triggered by intensified lactogenesis causing from a reduced blood level of steroid hormone in postpartum women and with increased prolactin concentrations. The incidence rate of breast engorgement throughout the world is 1:8000 and in India 1:6500. Objectives Of The Study: To assess the knowledge of primi mother’s regarding breast engorgement through pretest.To find out the effectiveness of structured teaching programme on knowledge regarding breast engorgement problem among primi mother’s through post-test.To find out the association between post-test knowledge score with selected demographic variables. Materials And Methods : The research approach used in the present study is quantitative research approach and the research design is one group pretest and post test design is chosen for conducting the study , where there is no randomization and control group . In this design all the subjects were selected by convenience sampling technique and were given a pre-test and then post-test were conducted after they receive an intervention. The setting of the study were selected hospitals of Rohtas District. The target population comprises of all the primigravida mothers . The accessible population in this study are all the primigravida mothers in selected hospitals of rohtas district . Structured questionnaire was prepared containing a set of questions , were asked by the sample. The investigator collected the data from the 50 primigravida mothers , who came for antenatal checkup or who was admitted in ward of Sadar Hospital and NMCH. Results: Nearly 70% of the mothers are of the age group 19-25 years , 30% of the age group 26-35 years, no mother are below age of 18 years and no mothers are above 35 years.About 22% of the mother are not having any formal education, 8% of the mother’s qualification was diploma, 50% of them are graduated , 6% are postgraduated and 14% have other qualification.Approx. 92% of the primigravida mothers are housewife , 3% are teacher and 1% have other occupation.About 40% of the mothers belong to nuclear family , 50% are from joint family and 10% of mothers belong to extended family. About 92% of the primi mother are hindu and remaining 8% to muslim religion.About 2% of the primi mothers have previous information from internet , 4% have previous information from books and 94% have previous information from health professionals.The mean score of concept of breast engorgement is raised from 8.74 (SD=2.365) in pretest( Margin of error = 8.74 ±0.655 at 95% confidence interval ) to 17.58 ( SD=1.69) in post-test ( Margin of Error = 17.58 ± 0.468 at 95% confidence interval ) . The t test computed between the pre-test and post-test knowledge of primigravida mothers ( t=22.7870) was highly significant at 1% level. Conclusion: The obtained findings of the study led to the following conclusions:Majority of the primigravida mothers suffered from the breast engorgement. Deficit of knowledge regarding prevention and management of breast engorgement existed in varying degree of primigravida mothers in all the learning need area.

Metoclopramide for Milk Production in Lactating Women: A Systematic Review and Meta-Analysis.

BackgroundBreastfeeding is recognized as the optimal form of nutrition for the physical and neurological development of infants and is considered the most significant way to prevent child mortality. This study aimed to assess the effectiveness of metoclopramide for enhancing milk production in lactating women.MethodsWe searched the Cochrane Central Register of Controlled Trials and MEDLINE for randomized controlled trials comparing metoclopramide with a placebo, no treatment, or other galactagogue drugs. We included breastfeeding women with term or preterm infants.ResultsWe retrieved 164 records from our search of the electronic databases and 20 records from other sources. Eight trials involving 342 lactating women that used metoclopramide were included in this review after assessing the eligibility criteria. The meta-analysis of these trials revealed that metoclopramide did not increase the milk volume of the intervention groups compared to that of the control groups. There was a significant increase in the serum concentrations of prolactin when the mothers were administered metoclopramide. No significant adverse events were reported.ConclusionMetoclopramide did not improve milk production in lactating women. Therefore, we do not recommend using metoclopramide to increase milk production in lactating women.

Long‐term use of prolactin‐increasing antipsychotics linked to breast cancer risk

Long‐term exposure to prolactin‐increasing antipsychotics increased risk of breast cancer in a case‐control study of women with schizophrenia. Use of antipsychotics that do not increase prolactin concentrations was not associated with an increased risk.

Relationship between clinical signs and hormonal analytical findings in bitches with lactatio sine graviditate.

Lactatio sine graviditate of the bitch can become clinically relevant in particularly severe manifestations. The aim of the study was to relate the hormone pattern consisting of progesterone (P4), estradiol 17β (E2) and prolactin to the time of occurrence of lactatio sine graviditate in the course of metoestrus and anoestrus as well as to its symptomatology. Sixty-eight bitches with apparent lactatio sine graviditate were divided into 3 groups according to their cycle status. All bitches were examined for gynaecological findings. Furhtermore, their blood progesterone, oestrogen, and prolactin concentrations were determined and compared with the 133-day hormone profile of 7 control animals. Lactatio sine graviditate occurring in early metoestrus was characterised more by a shifted P4:E2 ratio than by hyperprolactinaemia. Overall, the prolactin concentration in the peripheral blood was significantly increased. Analysis of the individual cases revealed that hyperprolactinaemia was present to varying degrees. It could be detected in almost all bitches that showed full symptomatology at the end of metoestrus or at the beginning of anoestrus. Only then clinical signs correlated with an increased prolactin concentration in the peripheral blood. In most cases, the estradiol-17β concentration was within the reference range. The study indicates that the administration of prolactin inhibitors alone is not indicated in all cases of lactatio sine graviditate and that the timepoint of onset of the clinically relevant symptoms and the current prolactin level should be taken into account in the treatment of affected bitches.

A Prepubertal Girl with Delusions of Pregnancy.

A Prepubertal Girl with Delusions of Pregnancy.

The association between prolactin concentration and aggression in female patients with schizophrenia

Objectives This study assessed the association between serum prolactin (PRL) concentration and aggression in female patients with schizophrenia. Methods Female patients with schizophrenia (N = 120) were diagnosed using SCID-5 based on the DSM-5 criteria. They were sampled at the University Psychiatric Hospital Vrapce during the period from March 2017 to March 2019. Aggression was evaluated using the Positive and Negative Syndrome Scale (PANSS), and Overt Aggression Scale (OAS). Patients were subdivided into aggressive and non-aggressive groups. PRL was determined in serum using electrochemiluminescence (ECLIA) method. Results Aggressive patients with schizophrenia had significantly (p < 0.0001) increased PRL concentration compared to non-aggressive patients. Higher PRL concentration was significantly (p < 0.0001) associated with pronounced aggressive symptoms determined by the OAS scores. When patients were subdivided into those who were treated with risperidone, haloperidol, paliperidone, amisulpride, and a group that was not treated with these antipsychotics, aggressive patients in both groups had significantly higher PRL concentrations than non-aggressive patients. Higher antipsychotic dose was related to increased PRL concentration (p = 0.004). Conclusions Our findings suggest that higher PRL is significantly associated with aggression, irrespective of the antipsychotic medication, in female patients with schizophrenia.

Paeoniflorin ameliorates antipsychotic-induced hyperprolactinemia in rats by attenuating impairment of the dopamine D2 receptor and TGF-β1 signaling pathways in the hypothalamus and pituitary

Ethnopharmacological relevancePaeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. AimTo examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. Materials and methodsHyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-β1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined. ResultsPaeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-β1 and its downstream genes, type II TGF-β receptor, type I TGF-β receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-β1 concentration and hepatic TGF-β1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-β1 signals in MMQ cells were attenuated. ConclusionsThis study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-β1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.

Effects of milking frequency and domperidone injections on milk production and prolactin signaling in the mammary gland of dairy cows

Eleven mid-lactation Holstein cows were milked twice daily during the first 2 experimental weeks. During wk 3 to 10, the cows were differentially milked: right quarters were milked thrice daily (3×) and left quarters were milked once daily (1×). During wk 11 to 14, all quarters were milked twice daily. After 4 wk of differential milking, the cows received daily i.m. injections of the dopamine antagonist domperidone (DOMP; 300 mg; n = 6) or of dimethyl sulfoxide as the control (CTL; n = 5) for 8 wk (wk 7-14). During the differential milking period (wk 3-6), milk production was greater for quarters milked 3× than for those milked 1× but did not differ between DOMP and CTL cows. During the differential milking + injection period (wk 7-10), milk production continued to differ according to milking frequency. However, DOMP injection did not have an effect or interact with milking frequency on milk production. During the injection period (wk 11-14), milk production remained greater in the quarters previously milked 3× and milk production increased in DOMP injected cows but not in CTL cows. Injections of DOMP increased prolactin concentration, which was greater in the serum of DOMP cows than in that of CTL cows during the differential milking + injection and the injection periods. The expression of genes that are directly related to milk synthesis (CSN2, LALBA, and ACACA) was greater in the 3× quarters than in the 1× quarters. In addition, DOMP increased CSN2 expression during the injection period. The expression of both isoforms of the PRLR gene was greater in the 3× quarters during the differential milking + injection and the injection periods. At the protein level, injections of DOMP tended to increase the number of long PRLR isoform during the differential milking + injection period. The number of short PRLR isoform was greater in the 1× quarters than in the 3× quarters during the differential milking, the differential milking + injection, and the injection periods. The total amount of STAT3 protein was greater in the 1× quarters during the differential milking and the differential milking + injection periods. The amount of phosphorylated STAT3 protein was greater in the 1× quarters during the differential milking period. The total amount of phosphorylated STAT5 protein was greater in the 3× quarters during the differential milking and the differential milking + injection periods. The results of this experiment support the hypothesis that the responsiveness of the mammary gland to PRL is modulated by milking frequency, although the underlying mechanism remains to be determined.

PSI-7 Effects of sustained hyperprolactinemia in late gestation on mammary development of gilts

Abstract This project sought to determine the effects of sustained hyperprolactinemia on mammary development in late-pregnant gilts. Gilts were divided into 3 groups on day 90 of gestation to receive i.m. injections of: 1) canola oil (CTL, n = 18) until day 109 of gestation, 2) domperidone (dopamine receptor antagonist) until day 96 (T7, n = 17) or, 3) domperidone until day 109 (T20, n = 17). Treated gilts also received domperidone orally from days 90 to 93. Blood was sampled on days 97 and 110 for prolactin and IGF-1 assays. Mammary glands were collected at necropsy on day 110 for compositional and cell proliferation analyses. The MIXED procedure of SAS was used for statistical analyses. On day 97 of gestation, prolactin concentrations were greater for T20 and T7 than CTL gilts (19.0, 18.9 and 6.0 ± 1.6 ng/mL, respectively, P &amp;lt; 0.001), and were also greater for T20 than T7 and CTL gilts on day 110 (21.7, 8.9 and 10.0 ± 1.5 ng/mL, respectively, P &amp;lt; 0.001). Concentrations of IGF-1 were greater for T7 and T20 than CTL gilts on day 97, and were greater for T20 vs T7 and CTL gilts on day 110 (P &amp;lt; 0.05). There were no effects of treatment (P &amp;gt; 0.1) on parenchymal or extraparenchymal tissue weights, or on cellular proliferation by immunohistochemistry for Ki67. Treatments did not alter concentrations of DM, fat or DNA (P &amp;gt; 0.1) in parenchyma, while concentrations of protein (P &amp;lt; 0.01) and RNA (P &amp;lt; 0.05) as well as total protein, RNA and DNA in parenchyma (P &amp;lt; 0.05) were lower in T20 than T7 or CTL gilts. Increasing prolactin concentrations for 7 or 20 d in late gestation had no beneficial effects on mammary composition, where sustained exposure for 20 d reduced metabolic activity.

Effects of sustained hyperprolactinemia in late gestation on mammary development of gilts

The objective of this project was to determine the effects of sustained hyperprolactinemia for 7 or 20 d on mammary development in late-pregnant gilts. On day 90 of gestation, gilts were assigned to one of 3 groups to receive intramuscular (IM) injections of (1) canola oil (CTL, n = 18) until day 109 ± 1 of gestation; (2) a dopamine receptor antagonist, domperidone (0.5 mg/kg of body weight [BW]) until day 96 ± 1 of gestation (T7, n = 17); or (3) domperidone (0.5 mg/kg BW) until day 109 ± 1 of gestation (T20, n = 17). Domperidone-treated gilts also received 100 mg of domperidone per os twice daily from days 90 to 93 of gestation. Blood was sampled on days 89, 97, 104, and 110 for prolactin (PRL), insulin-like growth factor 1 (IGF1), lactose, urea, and glucose assays. Mammary glands were collected at necropsy, on day 110, for compositional and cell proliferation analyses. Abundance of mRNA for selected genes was also determined in the mammary gland and the pituitary gland. On day 97 of gestation, PRL concentrations were 3 times greater for T20 and T7 than CTL gilts and were also greater for T20 than T7 and CTL gilts on days 104 and 110 (P < 0.001). Concentrations of IGF1 in T20 and T7 gilts were elevated relative to controls on days 97 and 104 and were greater for T20 vs T7 and CTL gilts on day 110 (P < 0.05). There were no treatment effects (P > 0.1) on parenchymal or extraparenchymal tissue weights, or on epithelial proliferation as measured by immunohistochemistry for Ki-67. Treatments did not alter concentrations of dry matter (DM), fat, or DNA (P > 0.1) in parenchyma. Concentrations of RNA (P < 0.05) and protein (P < 0.10) as well as total parenchymal protein, RNA, and DNA (P < 0.05) were lower, or tended to be, in T20 than T7 or CTL gilts. Hyperprolactinemia for 20 d in late gestation increased mRNA abundance of the milk protein genes beta-casein (CSN2) and whey acidic protein (WAP) (P < 0.05) in mammary parenchyma and also decreased mRNA abundance of the long form of the prolactin receptor (PRLR-LF). Increasing PRL concentrations for 7 or 20 d in late gestation had no beneficial effects on the composition of the mammary gland, and sustained exposure to domperidone for 20 d reduced metabolic activity either by a lower expression of the long form of the PRL receptor in mammary parenchymal tissue or, most likely, by the early involution of parenchymal tissue. In conclusion, results do not support the hypothesis that a sustained hyperprolactinemia in late gestation could enhance mammary development of gilts.

PO-01-068 Hormonal factors in patients with erectile dysfunction and diabetes

Diabetes damages vasculature and neurones and can therefore contribute to erectile dysfunction (ED). Although endocrine abnormalities are common in patients with ED, we hypothesised that they are less important in longstanding diabetes. Therefore, patients attending the out-patient diabetes clinic for ED treatment were included. Blood pressure, fasting serum glucose, cholesterol and triglyceride levels were measured together with TSH, LH, FSH, prolactin and testosterone level. Ninety-five consecutive patients were analysed. They were 51+/-9 years old and had a longstanding diabetes (12 +/-8 years). 22 (23%) patients had type 1 diabetes, 70 (74%) patients had type 2 diabetes and 3 (3%) patients had other types of diabetes. 73% of patients had established peripheral polyneuropathy and 49% had macrovascular disease. In 19% ED was due to a neurological cause, in 31% to a vascular cause, in 36% to a combined neuro-vascular cause, in 11% to a psychological cause and in 3% to an iatrogenic cause. Only 1 patient had lower testosterone level, 5 patients had increased LH and 17 patients had increased FSH. Three patients had increased TSH and 1 patient had increased prolactin concentration. In patients with complete vs. partial ED there was no significant difference in hormone status. Patients with neurogenic cause of ED had a higher serum testosterone level compared to patients with vascular (28,6 +/-12,2 vs. 20,2 +/-7,4 nmol/l) or combined (22,5 +/-8,0 nmol/l; p=0,029) cause. Night-time erection was associated only with shorter duration of ED (p=0,05) but with none of the hormonal or metabolic variables investigated.

Effect of prolactin on penile erection: a cross-sectional study.

Although elevated prolactin levels have been shown to inhibit penile erection, the relationship between prolactin and erection of the penile tip or base has not been extensively researched. We therefore investigated the prolactin's effects on erection of the penile tip and base, with a cross-sectional study of 135 patients with erectile dysfunction, based on scores of ≤21 on the International Index of Erectile Function-5. All patients were tested for nocturnal penile tumescence, blood pressure, serum glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, testosterone, and progesterone. Univariate and multivariate analyses were used to assess the associations between prolactin levels and erection at the penile tip and base. We found no obvious relationship between erection time at penile tip and prolactin levels, but observed a negative correlation between base erection time and prolactin level (hazard ratio: −2.68; 95% confidence interval [CI]: −5.13–−0.22). With increasing prolactin concentration, multivariate analysis showed obvious reduction in base erection time among patients with normal Rigiscan results (hazard ratio: −3.10; 95% CI: −7.96–1.77; P < 0.05). Our data indicate that prolactin inhibits penile erection, particularly at the penile base. In addition, when the effective erection time of the penile base lasts longer than 10 min, prolactin has a more obvious inhibitory effect on penile base erection.

Cooperative Synthesis of Dopamine in Rat Mediobasal Hypothalamus as a Compensatory Mechanism in Hyperprolactinemia.

Dopamine (DA), synthesized in the mediobasal hypothalamus by dopaminergic neurons containing two enzymes of DA synthesis - tyrosine hydroxylase and decarboxylase of aromatic L-amino acids, or by monoenzymatic non-dopaminergic neurons containing one DA synthesis enzyme in cooperation, is known to have an inhibitory effect on prolactin secretion. Deterioration of this inhibitory control leads to an increase in prolactin concentration in the blood and to the development of hyperprolactinemia syndrome. In a rat model of hyperprolactinemia induced by administration of a neurotoxin causing degeneration of dopaminergic and noradrenergic neurons, the level of DA first decreases, leading to an increase in prolactin level (decompensation stage), while later both levels are restored to normal (compensation stage). However, the mechanism of such compensation is still not clear. The aim of the present study was to analyze whether the increase in cooperative synthesis of DA by monoenzymatic neurons during hyperprolactinemia is a manifestation of a compensatory mechanism representing a particular case of neuroplasticity. The level of cooperative synthesis in the hyperprolactinemia model and in the control was estimated as the level of synthesis of DA and L-dihydroxyphenylalanine (L-DOPA)- an intermediate product of DA synthesis, when L-DOPA transfer from neurons containing tyrosine hydroxylase into neurons containing aromatic L-amino acid decarboxylase is inhibited. The level of DA synthesis during the decompensation stage was not changed, while during the compensation stage it was lower than the control. Along with a reduction in DA level, during the compensation stage an increase in the extracellular L-DOPA level in the medium was detected. Thus, the compensation of DA deficiency after degeneration of dopaminergic neurons in the mediobasal hypothalamus is due to the increase in cooperative synthesis of DA by monoenzymatic neurons containing one of the complementary enzymes of the DA synthesis pathway.

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.

The dopamine antagonist domperidone increases prolactin concentration and enhances milk production in dairy cows

In previous studies, our team showed that the inhibition of prolactin (PRL) secretion by the dopamine agonist quinagolide reduces milk production in dairy cows. The objective of this study was to determine the effects of administration of a dopamine antagonist on basal and milking-induced PRL concentrations in blood and on milk production during positive energy balance and feed restriction in dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections of either domperidone (300mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9), for 5wk. During wk 5, all cows were fed at 65% of their dry matter intake in the previous week. Blood and milk samples were collected before (for blood) and during (for milk) the a.m. milking thrice weekly from d −9 to 41 (8d after the last injection). In addition, blood samples were collected during the a.m. milking on d −1 (before the first injection), and on d 1, 28, and 34. Basal PRL concentration was similar in both groups before the start of the treatments. Domperidone injections caused a gradual increase in basal PRL concentration. Feed restriction reduced basal PRL concentration in both the CTL and DOMP cows, but PRL concentration remained higher in the DOMP cows. Prolactin concentration remained elevated in the DOMP cows 7d after the last injection. The milk concentration of PRL increased during the DOMP treatment, but the increase was smaller than that observed in serum. In the CTL cows, the milking-induced PRL release above the premilking concentration was similar on d −1, 1, and 28 but was reduced during feed restriction. In the DOMP cows, the milking-induced PRL release was similar on d −1 and 1 but was reduced on d 28 and 34. Milk production was similar for both groups before the treatments started but was greater in the DOMP cows during the treatment period, at 2.9±0.6 and 2.4±0.6kg/d greater during wk 3 and 4 of treatment, respectively. Milk production declined in both groups during feed restriction but remained higher in the DOMP cows. Milk production became similar again for both groups after the last injection. In addition, dry matter intake was increased by DOMP. These results support the hypothesis that PRL is galactopoietic in dairy cattle.

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation

The sodium coupled neutral amino acid transporter 2 (SNAT2/SAT2/ATA2) is expressed in the mammary gland (MG) and plays an important role in the uptake of alanine and glutamine which are the most abundant amino acids transported into this tissue during lactation. Thus, the aim of this study was to assess the amount and localization of SNAT2 before delivery and during lactation in rat MG, and to evaluate whether prolactin and the dietary protein/carbohydrate ratio might influence SNAT2 expression in the MG, liver and adipose tissue during lactation. Our results showed that SNAT2 protein abundance in the MG increased during lactation and this increase was maintained along this period, while 24h after weaning it tended to decrease. To study the effect of prolactin on SNAT2 expression, we incubated MG explants or T47D cells transfected with the SNAT2 promoter with prolactin, and we observed in both studies an increase in the SNAT2 expression or promoter activity. Consumption of a high-protein/low carbohydrate diet increased prolactin concentration, with a concomitant increase in SNAT2 expression not only in the MG during lactation, but also in the liver and adipose tissue. There was a correlation between SNAT2 expression and serum prolactin levels depending on the amount of dietary protein/carbohydrate ratio consumed. These findings suggest that prolactin actively supports lactation providing amino acids to the gland through SNAT2 for the synthesis of milk proteins.