Basal Prolactin Research Articles

Mildly Higher Serum Prolactin Levels Are Directly Proportional to Cumulative Pregnancy Outcomes in in-vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

Hyperprolactinemia has long been considered detrimental to fertility due to irregularity of ovulation. Whether mild hyperprolactinemia should be corrected before initiating an in-vitro fertilization/intracytoplasmic sperm injection cycle (IVF/ICSI) has not been determined; this study aimed to examine how different levels of prolactin affect IVF outcomes. A total of 3,009 patients with basal prolactin level <50 ng/mL undergoing IVF/ICSI cycles for tubal or male factors were recruited in this study. Patients diagnosed with anovulation owing to polycystic ovarian syndrome or hyperandrogenism were ruled out. Pregnancy outcomes were compared between patients with basal prolactin levels higher or lower than the median level of prolactin (16.05 ng/mL). Multifactor analyses were carried out among four subgroups depending on different prolactin levels. Repeated-measures analysis of variance was used to explore the relationship between the ascending trend of prolactin levels over ovarian stimulation and the corresponding cumulative pregnancy outcomes. There were significantly higher numbers of oocytes (9 vs. 8, P = 0.013) and embryos (6 vs. 5, P = 0.015) in patients with basal prolactin higher than 16.05 ng/mL. Basal prolactin higher than 30 ng/mL was positively related to cumulative clinical pregnancy, and a level higher than 40 ng/mL was a good indicator for the cumulative live birth rate. Throughout ovarian stimulation, the prognosis of pregnancy improved with increasing prolactin levels. Patients with better cumulated pregnancy outcomes had significantly higher prolactin levels as well as a profoundly increasing trend during the stimulating process than those who did not conceive. For patients who underwent the gonadotropin-releasing hormone agonist long protocol IVF/ICSI treatment, a slightly higher prolactin level during the controlled ovarian hyperstimulation protocol was a positive indicator for cumulated pregnancy/live birth rates.

Increased Breastfeeding Frequency Enhances Milk Production and Infant Weight Gain: Correlation with the Basal Maternal Prolactin Level.

Background: Breastfeeding is an important health concern for postpartum women. Objective: This study aimed to investigate the effect of breastfeeding frequency on the level of serum prolactin (PRL), milk intake, and infant weight gain. Materials and Methods: The time and duration of each breastfeeding episode were recorded by participants from day 1 to 28 postpartum. According to their diaries, we divided participants into the low-frequency breastfeeding group (Group I; <10 breastfeeding episodes/day) and high-frequency breastfeeding group (Group II; >/ = 10 breastfeeding episodes/day). A total of 23 mother-infant pairs were enrolled; blood samples were drawn between 1600 and 1800 hours. The PRL levels were examined using the DPC Immulite system. Results: Overall, 71.8% (23) of the enrolled mother-infant pairs completed the follow-up. Infant birth weight was higher in Group II than in Group I (3275.6 ± 93.3 g versus 2918 ± 82.1 g). On day 28 postpartum, infants in Group II ingested significantly more milk per feeding (71.6 ± 4.0 mL versus 54.1 ± 5.2 mL) and gained more weight from birth (142.9% ± 4.5% versus 130.2% ± 2.4%) compared with those in Group I. The mothers of Group II had significantly higher basal serum PRL levels (116.4 ± 11.8 ng/mL versus 72.7 ± 7.77 ng/mL), but a significantly lower increase in PRL postsuckling (168.5% ± 23.1% versus 291.6% ± 37.6% of basal PRL). The frequency of suckling was positively correlated (r = 0.5) with the basal PRL level. Moreover, infant weight gain was significantly higher in male (144.7% ± 4.7%) than in female (132.3% ± 2.9%) infants. Conclusions: Increase in frequency of breastfeeding of over 10/day is associated with baseline PRL levels and increased milk production and weight gain. These results provide useful information for breastfeeding women.

SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases

Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (<300 for male, <600 for female). Three patients have hypopituitarism at presentation, one after surgery and one remained eupitary 5 years after diagnosis. One developed late onset hypopituitarism 4 years after normalisation of prolactin levels. Three patients underwent debulking at presentation because of significant mass effects with obstructive hydrocephalus. In all patients cabergoline 1-1.5 mg/wk was started at diagnosis and gradually increased to 0.5 mg daily, aiming for normoprolactinemia. From May 2017 bromocriptine were given to these patients who continued to have hyperprolactinemia despite cabergoline 3.5-4mg/wk. Bromocriptine was commenced 1.25-5mg/day and gradually increased to 10 mg/day on top of cabergoline with careful monitoring of prolactin levels and side effects. Cabergoline was tapered down to 1.5-2mg/wk if prolactin levels remained stable between 2-3x normal while maintaining dose of bromocriptine. In M1, cabergoline was tapered off while maintaining bromocriptine 10mg/day with stable prolactin levels (~1000 mIU/L). In M2, normoprolactinemia was achieved after adding on bromocriptine and is currently on cabergoline 2mg/week and bromocriptine 10mg/day. In M3, whose prolactin were 4x normal value despite cabergoline 3.5mg/week, decreased 50% with bromocriptine 5 mg/day and remained stable when cabergoline reduced to 1.5mg/week. F1 had transphenoidal section twice due to failure of medical therapy. Her prolactin remained markedly elevated 10000-20000 mIU/L despite cabergoline 3.5 mg/week and bromocriptine 10mg/day, with persistent bitemporal hemianopia. F2 developed erythema nodosum after starting bromocriptine which was stopped and continued with cabergoline 1 mg/week. F3 showed partial response with 50% reduction in prolactin to 4485 mIU/L with bromocriptine 10 mg/day and cabergoline 1.5mg/week. In patients who underwent debulking, residual tumour remained unchanged. Two patients - tumour shrank 40% (F2) and 90% (M3) with medical therapy alone. In conclusion, adding on bromocriptine can be considered when high dose cabergoline is required for treatment of giant prolactinoma with careful monitoring. This reduces cabergoline dose which saves cost.

SAT-474 Giant Prolactinoma Case Series Assessing Response on Initial Dose of Cabergoline

Background: Giant prolactinomas (GPs) are rare representing 2-3% of prolactinomas and only ~ 0.5% of all pituitary tumors. Various definitions have been proposed for GP but commonly accepted criteria is tumor dimension of ≥4 cm. GP is often associated with very high prolactin (PRL) ranging 1,000 -100,000 ng/ml, significant extrasellar extension and no concomitant growth hormone or ACTH secretion. Patients predominantly present with neurological symptoms rather than endocrine dysfunction, and so the primary goal of treatment is amelioration of neurological symptoms. The literature search reveals approximately 190 papers on this topic and most are single case reports or series describing only unusual clinical manifestations. Hence, evidence based recommendations for treatment are lacking. Dopamine agonist (DA) is considered first line of therapy, as these tumors are highly sensitive to medical therapy. Surgery and radiation may be warranted in special situations. Low starting doses of cabergoline (CAB) are generally recommended due to concern for complications of apoplexy and cerebrospinal fluid (CSF) leak from rapid tumor shrinkage. However, no recommendations for a specific starting dose exist. Objective: Individual tumor and hormonal response were assessed on 15 patients (pts) with GP on low dose CAB; 0.25-0.5 mg weekly to determine the effectiveness of DA therapy. Methods: 15 GP pts from two tertiary care centers, meeting the diagnostic criteria mentioned above, were reviewed. Reduction in tumor volume and maximal tumor diameter along with PRL, after initiation of CAB, at or before 6 months and 1 year post diagnosis, was calculated. Results: Presenting symptom: visual disturbance (56%), headache (20%), apoplexy (13%) and incidental finding (6%). Mean age at diagnosis: 61 years. Male to Female: 4: 1. Basal prolactin concentration: >2000 ng/dl (12/15pts), and > 900 ng/ml (2/15). Initial total CAB dose/week: 0.25-0.5 mg (13/15) and 1-2 mg (2/15). Cranial surgery: 4/15. Complications: CSF leak (1/15). Tumor volume assessed at 6 months (11/15) and 1 year (4/15) along with decrease in maximum tumor diameter in the same period of time. PRL assessed at or before 6 months (13/15) and at 1 year (2/15). Improvement in tumor size occurred promptly even with low dose CAB (0.25-0.5mg/week). 100% of patients initiated on low dose CAB responded to therapy. Mean reduction in tumor volume at or before 6 months was 47% in 11/15, and 52% at 1 year (10/15). Mean decrease in maximal tumor dimension was calculated as 0.95 cm at 6 months (12/15) and 1.4 cm at 1 year (9/15). The overall prolactin response rate at or before 6 months was > 90% in 7/15 patients (53%) and >50% in 11/15 patients (73%). Conclusion: Our data confirms excellent tumor response to low dose cabergoline therapy. Dose as low at 0.25 mg twice weekly is proven to be effective, leading to decrease in both tumor volume and PRL levels.

Effect of endometrial scratch using a Pipelle catheter on recurrent implantation failure with intracytoplasmic sperm injection

Back ground In the last two decades, assisted reproductive technology procedures for culturing and transferring embryos have been continually improved, but the clinical pregnancy rate has not improved substantially over the last 10 years. The most important cause for implantation failure is embryo quality or uterine receptivity, but remains unexplained in many cases. About 75% of conceptus are lost before or at the time of implantation. Aim This work aims to assess the effect of endometrial scratch (ES) using a Pipelle catheter on the outcome of intracytoplasmic sperm injection (ICSI) in patients with recurrent implantation failure. Patients and methods The current study included 130 patients who were divided into two equal groups of 65 patients each. In the scratch group, endometrial local scratch using a Pipelle biopsy catheter on the mid luteal phase of spontaneous menstrual cycle before the ICSI procedure was performed, whereas the control group did not undergo ES. ICSI failure was recorded two or more times in each group. Results In the current study, there were no statistically significant differences between the two groups in age, gravidity and parity, type, duration of infertility, and the number of previous ICSI trials. However, the BMI was higher in the control group. In the current study, there were no statistically significant differences between the two groups in basal hormonal profile follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, estradiol, and anti-Mullerian hormone. In this study, there was highly significant increase in the pregnancy rate in the scratch group than the nonscratch group. The number of pregnant cases in the scratch group was 36 (55.4%), whereas in the control group, it was 21 (32.3%), with a highly significant P value of 0.008. In this study, there was no statistically significant difference between positive and negative pregnancy in the basal hormonal profile, except anti-Mullerian hormone and follicle-stimulating hormone levels, P values of 0.040 and 0.000. Conclusion ES in the cycle before the ICSI cycle improved the chemical and clinical pregnancy rates compared with ICSI performed without ES in cases of recurrent implantation failure. It seems that increasing pregnancy rates could be because of the local inflammatory reaction elicited by the endometrial sampling procedure.

Secretory tumors of the pituitary gland: a clinical biochemistry perspective.

The pituitary gland is responsible for the production and/or secretion of various hormones that play a vital role in regulating endocrine function within the body. Secretory tumors of the anterior pituitary predominantly, pituitary adenomas, collectively account for 10%-25% of central nervous system tumors requiring surgical treatment. The most common secretory tumors are prolactinomas, which can be diagnosed by basal prolactin levels. Acromegaly can be diagnosed by basal insulin growth-like factor 1 levels and the failure of growth hormone (GH) to suppress during an oral glucose tolerance test. Cushing disease can be diagnosed by demonstrating hypercortisolemia evidenced by increased salivary cortisol levels in the evening, increased urine free cortisol excretion and failure of plasma cortisol to suppress following oral dexamethasone given overnight (1.0 mg). We also discuss the diagnosis of the rarer thyroid-stimulating hormone and gonadotrophin secretory tumors. Morbidity is associated with tumor occurrence, clinical sequelae as well as the related medical, surgical and radiological management. This review focuses on the pathogenesis of secretory tumors of the anterior pituitary with emphasis on molecular mechanisms associated with tumorigenesis and the major role of the clinical chemistry laboratory in diagnosis and management of these tumors.

Changes in serum prolactin level during intracytoplasmic sperm injection, and effect on clinical pregnancy rate: a prospective observational study

BackgroundTransient hyperprolactinemia was proven to adversely affect the outcome of IVF. We aimed to identify changes in serum prolactin levels in patients undergoing ICSI, and to evaluate the effect of these changes on the clinical pregnancy rate.MethodsA prospective observational study included 90 patients scheduled for ICSI cycles. In each case 4 serum samples were collected during the cycle (midluteal, before ovum pick up procedure (OPU), 2 h after OPU, and before embryo transfer). Serum prolactin level was determined by immunoassay each time.ResultsThe sample collected 2 h after OPU had a mean difference of 25.8 ± 2.8 ng/ml compared to the basal serum prolactin (p < 0.01). In comparison to other samples, this highlighted a significant hyperprolactinemia occurring after OPU, and resolving before embryo transfer. No statistically significant difference between the different serum prolactin samples amongst the pregnant and non pregnant patients. There was a significant positive pearson correlation between the prolactin levels before OPU, and the presence of higher quality embryos (r = 0.274, p = 0.019).ConclusionIn normoprolactinemic women transient hyperprolactinemia is identified in patients undergoing ICSI, and it doesn’t affect the clinical pregnancy rates. A positive correlation was identified between higher quality embryos, and serum prolactin level before OPU.Trial registrationClinicalTrials.gov Identifier: NCT02292953, First received: November 10, 2014.

Olfactory marker protein regulates prolactin secretion and production by modulating Ca2+ and TRH signaling in lactotrophs

Olfactory marker protein (OMP) is a marker of olfactory receptor-mediated chemoreception, even outside the olfactory system. Here, we report that OMP expression in the pituitary gland plays a role in basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) production and secretion. We found that OMP was expressed in human and rodent pituitary glands, especially in PRL-secreting lactotrophs. OMP knockdown in GH4 rat pituitary cells increased PRL production and secretion via extracellular signal-regulated kinase (ERK)1/2 signaling. Real-time PCR analysis and the Ca2+ influx assay revealed that OMP was critical for TRH-induced PRL secretion. OMP-knockout mice showed lower fertility than control mice, which was associated with increased basal PRL production via activation of ERK1/2 signaling and reduced TRH-induced PRL secretion. However, both in vitro and in vivo results indicated that OMP was only required for hormone production and secretion because ERK1/2 activation failed to stimulate cell proliferation. Additionally, patients with prolactinoma lacked OMP expression in tumor tissues with hyperactivated ERK1/2 signaling. These findings indicate that OMP plays a role in PRL production and secretion in lactotrophs through the modulation of Ca2+ and TRH signaling.

Reduction in basal plasma Adrenocorticotropic hormone (ACTH) and Prolactin during treatment with escitalopram for depression

Reduction in basal plasma Adrenocorticotropic hormone (ACTH) and prolactin during treatment with escitalopram for depression.

Effect of 17β-estradiol on milk production, hormone secretion, and mammary gland gene expression in dairy cows

Estradiol inhibits milk production in dairy cows. The present study evaluated the effect of 17β-estradiol (E2) injections on prolactin (PRL) secretion and the mammary gland response to this hormone. Eight mid-lactation cows were used in a crossover design. During each experimental period, the cows were injected daily with either E2 (2.5 mg) or soy oil (2.5 mL; control) for 7 d. For each period, blood and milk samples were collected from d -4 to 14 (relative to the first injection) to measure PRL, insulin-like growth factor-1, and cortisol concentrations. In addition, blood samples were collected during morning milking on d -4, 2, and 7 to determine the milking-induced PRL release. Mammary gland biopsies were collected on the last day of injections. Milk fat samples were collected from d 1 to 7 and on d 14. The mRNA levels of genes encoding proteins related to mammary activity (α-lactalbumin, β-casein, and acetyl-coenzyme A carboxylase), apoptosis (Bax, Bcl2, and caspase-3), PRL receptors (PRLR; long and short forms), signal transducer and activator of transcription 5 (STAT5A and STAT5B), and suppressors of cytokine signaling (SOCS2 and SOCS3) were evaluated by real-time reverse transcription PCR using RNA extracted from milk fat and mammary biopsies. Milk production was decreased moderately (about 9%) by E2 injections during the treatment period. Estradiol injections increased basal PRL levels in serum and milk but did not affect milking-induced PRL release. Estradiol injections increased the plasma concentration of insulin-like growth factor-1 but did not affect cortisol concentration during the treatment period. In mammary tissue, the expression of Bcl2 was downregulated, whereas that of STAT5A and B and the Bax:Bcl2 mRNA ratio was higher during E2 injections. The total STAT5 protein content in mammary tissue was elevated by E2 injections. We found no significant difference observed for the other genes in mammary tissue or milk fat. The present data do not support the contention that E2 injections inhibit milk production by interfering with PRL signaling, but enhanced basal PRL concentration and STAT5 gene expression in mammary tissue.

Seasonal Assessment of Duration of Prolactin Suppression Following Cabergoline Treatment in Mares: Unstimulated Versus Sulpiride and Thyrotropin-Releasing Hormone-Stimulated Responses

Experiments 1 through 4 were performed to test the hypothesis that season affects the duration of prolactin suppression by a single injection of the dopaminergic agonist, cabergoline. In each, six mares received cabergoline intramuscularly and four received the vehicle. The protocol was repeated around the vernal equinox, summer solstice, autumnal equinox, and winter solstice. In all experiments, cabergoline suppressed (P < .01) prolactin for at least 5 days; concentrations in fall and winter were naturally low; thus, treatment effects were harder to detect. Experiments 5 and 6 tested whether basal (unstimulated) prolactin concentrations recovered from cabergoline suppression faster (earlier) than secretagogue-induced prolactin secretion. In July, five mares each were treated with either compounded cabergoline or cabergoline in oil; four others received oil. Cabergoline suppressed (P < .0001) prolactin in both treated groups for approximately 6 days. Prolactin in daily samples returned to control levels thereafter, whereas low-dose sulpiride-stimulated secretion remained suppressed by >50% at 11 days after treatment. In the last experiment, treatment with cabergoline or oil (n = 6 mares each) in October followed by thyrotropin-releasing hormone (TRH) challenges resulted in similar responses to those in experiment 5; TRH-induced prolactin responses were still suppressed (P < .05) on day 11. In conclusion, little seasonal variation in duration of prolactin suppression in response to cabergoline was detected. In general, secretagogue-induced secretion is suppressed much longer than basal secretion. This dichotomy may indicate at least two subpopulations of lactotropes regulated differentially by dopamine input.

Effects of photoperiod modulation and melatonin feeding around drying-off on bovine mammary gland involution

The risk for a dairy cow to acquire new intramammary infections is high during the transition from lactation to the dry period, because of udder engorgement and altered immune functions. Once the gland is fully involuted, it becomes much more resistant to intramammary infections. Therefore, strategies to depress milk yield before drying-off and accelerate the involution process after drying-off could be beneficial for udder health. The objective of this study was to assess the effect of photoperiod manipulation and melatonin feeding from 14 d before to 14 d after drying-off on the speed of the involution process. Thirty Holstein cows in late lactation were randomly allocated to one of the following treatments: (1) a long-day photoperiod (16 h of light: 8 h of darkness), (2) a short-day photoperiod (8 h of light: 16 h of darkness), and (3) a long-day photoperiod supplemented by melatonin feeding (4 mg/kg of body weight). Milk and blood samples were collected on d -26, -19, -12, -5, -1, 1, 3, 5, 7, 10, and 14 relative to the last milking to determine concentrations of mammary gland involution markers and serum prolactin. Additional blood samples were taken around milking on d -15, before the start of the treatments, and on d -1, before drying-off, to evaluate the treatment effects on milking-induced prolactin release. The short-day photoperiod slightly decreased milk production and basal prolactin secretion during the dry period. The milking-induced prolactin surge was smaller on d -1 than on d -15 regardless of the treatments. Lactoferrin concentration, somatic cell count, and BSA concentration as well as matrix metalloproteinase-2 and -9 activities increased in mammary secretions during the first 2 wk of the dry period, whereas milk citrate concentration and the citrate:lactoferrin molar ratio decreased. The rates of change of these parameters were not significantly affected by the treatments. The long-day photoperiod supplemented by melatonin feeding did not affect milk production, prolactin secretion, or mammary gland involution. Under the conditions in this study, photoperiod modulation and melatonin feeding did not appear to affect the rate of mammary gland involution.

Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells

The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells.

Basal prolactin levels in rat plasma correlates with response to antidepressant treatment in animal model of depression

Prolactin (PRL) has been shown to be altered by psychotropic drugs, including antidepressant drugs (ADs). Many studies have focused on the response to antidepressant treatment (especially related to the serotonergic system) using the fenfluramine test (PRF), however some data suggest lack of correlation between PRF and prediction of clinical response to ADs.In our study we have investigated the hypothesis that basal plasma level of prolactin is a better predictor of antidepressant treatment. We have used Chronic Mild Stress (CMS) – the animal model of depression. Rats are exposed to CMS in combination with imipramine (IMI) treatment for 5 consecutive weeks. Blood samples were collected from the rat tail vein three times: before the CMS procedure, after 2 weeks of stress and after the complete CMS procedure (after 5 weeks of stress and IMI treatment). The PRL level in plasma was determined using the commercially available ELISA kit.In CMS, anhedonia in rats is manifested by reduced consumption of sucrose solution while administration of antidepressant drugs reverses anhedonia. Some animals (ca.30%) did not respond to antidepressant therapy and were considered treatment-resistant. There was no correlation between basal PRL levels and stress response, however, from the results obtained by Spearman Rank Correlation analysis we have observed a significant negative correlation between basal PRL levels before the CMS procedure and behavioral response to IMI administration. The obtained results indicate that the basal PRL level in rat plasma correlates with a good response to treatment in the animal model of depression.

Relationship between glucocorticoids and prolactin during mammary gland stimulation in dairy cows

The objectives of this study were to determine the role of glucocorticoids in the regulation of prolactin (PRL) release induced by mammary gland stimulation and to investigate whether the milk depression induced by glucocorticoids in dairy cows is due to a decrease in PRL release. In experiment 1, 8 dairy cows were used in a 4 × 4 Latin square design. Four hours after the morning milking, the cows received 1 of the following treatments: (1) a 5-min manual stimulation of the mammary gland; (2) an i.v. injection of 1 mg of dexamethasone; (3) 2 infusions of 2.5 g of metyrapone (an inhibitor of cortisol biosynthesis) in the omasum 4 and 2 h before a 5-min stimulation of the mammary gland; or (4) no treatment. Sixty minutes later, the mammary gland of each cow was stimulated for 5 min. Blood samples were collected from 20 min before to 120 min after the start of the treatment. When the mammary gland was stimulated twice in 60 min, less PRL and cortisol were released during the second stimulation. Metyrapone did not affect PRL or cortisol release. Dexamethasone decreased serum cortisol concentration but did not affect PRL concentration. In experiment 2, 16 cows were used in a crossover experimental design consisting of 2 experimental weeks separated by 1 resting week. During the first week, cows were treated as follows: (1) 4 cows were injected with 0.5 g of domperidone (a PRL secretagogue) in canola oil on d 1 and 2 and 20 mg of dexamethasone on d 1; (2) 4 cows were injected with 0.5 g of domperidone on d 1 and 2; (3) 4 cows were injected with canola oil on d 1 and 2 and with 20 mg of dexamethasone on d 1; and (4) 4 cows were injected with canola oil on d 1 and 2. During the second experimental week, the same 4 treatments were repeated, except the cows that did not receive dexamethasone in the first week received it on d 1 of the second week, and cows that did receive it in the first week did not receive it in the second week. On d 1 and 2 of each week, blood samples were collected during morning milking for PRL determination. Dexamethasone reduced milk production and decreased both basal and milking-induced PRL release. It also increased milk fat and protein percentages and decreased milk lactose content. Domperidone increased basal PRL levels in serum and milk but did not affect milk yield. Although we cannot rule out the possibility that inhibition of PRL secretion or reduction of mammary gland PRL responsiveness play a role in the inhibition of milk production by glucocorticoids, the fact that enhancement of PRL secretion by domperidone could not prevent the depression of milk yield suggests that other mechanisms are involved.

Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice.

Prolactin (PRL) is well characterized for its roles in initiation and maintenance of lactation, and it also suppresses stress-induced responses. Feeding a high-fat diet (HFD) disrupts activity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether PRL regulates HPA axis activation under HFD feeding is not clear. Male and female wildtype (WT) and PRL knockout (KO) mice were fed either a standard low-fat diet (LFD) or HFD for 12 weeks. Circulating corticosterone (CORT) levels were measured before, during, and after mice were subjected to an acute restraint stress or remained in their home cages as no stress controls. HFD feeding increased leptin levels, but the increase was lower in KO than in WT mice. All stressed female groups and only LFD-fed stressed males had elevated CORT levels compared to their no stress same-sex counterparts regardless of genotype. These results indicated that HFD consumption blunted the HPA axis response to acute stress in males but not females. Additionally, basal hypothalamic CRH content was lower in HFD than LFD males, but was similar among female groups. Furthermore, although basal CORT levels were similar among KO and WT groups, CORT levels were higher in KO mice than their WT counterparts during stress, suggesting that loss of PRL led to greater HPA axis activation. Basal PRL receptor mRNA levels in the choroid plexus were higher in HFD than LFD same-sex counterparts, suggesting activation of central PRL’s action by HFD feeding in both males and females. Current results confirmed PRL’s roles in suppression of the stress-induced HPA axis activation. Although HFD feeding activated central PRL’s action in both sexes, only the male HPA axis was dampened by HFD feeding.

Role of Estradiol in the Regulation of Prolactin Secretion During Late Pregnancy.

Estrogen action is necessary for evidencing the stimulatory action of mifepristone and naloxone on prolactin (PRL) secretion during late pregnancy. Our aim is to determine the mechanism mediating this facilitator action of estrogens. To investigate the hypothalamic mechanisms involved in estrogen actions in PRL secretion at the end of pregnancy, we measured the effect of pretreatment with the estrogen antagonist tamoxifen on the expression of tyrosine hydroxylase (TH), hormone receptors (ERα and β, PRs, PRLR(long)), and μ- and κ- opioid receptors (ORs) at mRNA (by semiquantitative RT-PCR) and protein (by western blot for TH, PRLR(long), ERα, PRs, μ- and ORs) levels in extracts of medial basal hypothalamus (MBH) and serum PRL, E2 and P4 levels (by RIA) in mifepristone- and naloxone-treated rats. Tamoxifen administration partially prevented PRL release induced by the combined treatment. TH expression diminished and ERα expression increased in mifepristone-treated rats at mRNA and protein levels and tamoxifen partially prevented these changes with no effect on PRs expression. Mifepristone increased PRLR(long) mRNA levels; this increase was blocked by tamoxifen. Combined tamoxifen and mifepristone treatment decreased μ- and k-ORs mRNA but not protein levels. In conclusion, E2 induces neuroadaptive mechanisms necessary to facilitate PRL release preceding delivery. Acting through ERα, E2 modulates hypothalamic dopaminergic neurons activity, regulating TH, μ- and κ-ORs and PRLR(long) expression, and is necessary for evidencing the effects of P4 withdrawal. Its presence on days 14 and 15 of pregnancy is crucial to facilitate the opioid system modulation of PRL secretion at the end of pregnancy in the rat.

Is there an effect of thyroid autoimmunity on the outcomes of assisted reproduction?

We aimed to evaluate the role of thyroid autoantibodies (TAA) on the outcomes of intracytoplasmic sperm injection-embryo transfer (ICSI-ET). A prospective case–control study was conducted in the in vitro fertilisation (IVF) centre of Suleymaniye Maternity Training and Research Hospital, Istanbul, Turkey between July 2013 and March 2014. A total of 49 (19.52%) TAA-positive and 202 TAA-negative patients were enrolled. Demographic characteristics and laboratory parameters were recorded. All patients underwent ICSI-ET. Thirty-one TAA-positive patients (32 cycles) and 121 TAA-negative patients (126 cycles) completed the study. Mean female age, body mass index (BMI), type of infertility, duration of infertility, antral follicle count (AFC), anti-Müllerian hormone (AMH), basal follicle stimulating hormone (bFSH), luteinising hormone (bLH), and oestradiol (bE2), prolactin and thyroid hormone profiles, male age and aetiology of infertility of both groups were similar (p > 0.05). There was no significant difference between groups in terms of duration and dose of gonadotropin (Gn) therapy, day of human chorionic Gn (hCG) administration, serum E2 and progesterone levels, number of collected oocytes, ratio of fertilisation, number of available embryos, positive pregnancy test, biochemical pregnancy, clinical pregnancy, ratio of miscarriage and ongoing pregnancy (p > 0.05). In conclusion, we failed to demonstrate a significant role of TAA on the outcomes of ICSI-ET in euthyroid patients. Further studies with larger numbers of participants are required to clarify these data.

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.

Serum macroprolactin levels in pregnancy and association with thyroid autoimmunity.

BacgroundTo assess the contribution of macroprolactin to high serum prolactin levels and their association with thyroid status and thyroid autoimmunity during pregnancy.Methods138 pregnant women who suspected of having thyroid dysfunction were studied and divided into three groups according to the thyroid status; group 1; euthyroidism (n 40), group 2; hypothyroidism (n 54), and group 3; hyperthyroid (n 44). Polyethylene glycol (PEG) precipitation method was used for detection of macroprolactin. A percentage recovery of 40 % or less is considered as macroprolactinemia. If macroprolactin was negative, the percentage of monomeric prolactin recovery (monoPRL %) after PEG precipitation was used for comparison between the groups.ResultsMacroprolactinemia was found in two patients (1.4 %) one from hypothyroid and other from euthyroid group. Basal prolactin levels in these patients were 400 and 403 ng/mL respectively. Referring to all patients, there was no correlation between PRL, macroPRL or monoPRL % with thyroid hormone status and also with the serum levels of thyroid antibodies (p > 0.05). A positive correlation was observed between the serum levels of PRL with TSH (p = 0.014 and r = 0.219), while a negative correlation was found with FT4 (p = 0.011 and r = −0.227).ConclusionsDespite the fact that serum prolactin levels were found to be high during pregnancy, the contribution of macroprolactin was found to be insignificant in our study. Unlike other auto immune diseases, we could not find any relationship between thyroid autoimmunity and PRL, macroPRL or monoPRL %. These results confirmed that measured prolactin was quite homogeneous during pregnancy.