PRL Concentrations Research Articles

Profiles of maternal origin factors during transition from embryonic diapause to implantation in roe deer.

The aim was to evaluate in female roe deer: (a) PAG mRNA relative abundance in endometrial uterine tissue for determination of the duration of embryonic diapause, (b) mRNA relative abundance of progesterone, estradiol, and prolactin (P4, E2, and PRL) receptors (PGR, ESR, and PRLR) during diapause and after implantation in the endometrium; (c) concentration of P4, E2, and PRL in the blood, and (d) a noninvasive method of hormone detection by measurement of P4 and E2 concentrations in feces. A total of fifteen individuals were obtained post mortem during hunting seasons and divided into three experimental groups (November, December, January). The results did not reveal mRNA relative abundance for PAGs in the endometrium or detectable PAG concentrations in the serum of all examined females. Concentration of PRL and mRNA relative abundance for PRLR long isoform in the endometrium was the highest in January (p<.01). mRNA relative abundance for PGR, P4 concentration in the endometrium, serum, and feces was the highest in January (p<.01). Endometrial origin PRL and P4 may be responsible for the termination of this process and pregnancy development after implantation.

159 Relationships among circulating prolactin concentrations, hair coat score, and weights of grazing cows

Abstract Prolactin (PRL) is a pleiotropic protein hormone synthesized and released from the anterior pituitary. Concentrations of PRL can serve as a biomarker of cattle exposure to ergot alkaloids. Our objective was to determine relationships among prolactin concentrations, hair coat score, and body weights of non-lactating crossbred beef cows (n = 71). Cows were weighed, hair coat scored (1 = 100% shed, and 5 = 0% shed), and blood samples collected in May, June, and July. Cows were grazing mixed grass pastures that included native endophyte-infected tall fescue. Serum PRL concentrations were determined by validated RIA. Based on May samples, cows were categorized as high (n = 11; 159 ± 29 ng/mL PRL), medium (n = 48; 51 ± 4 ng/mL PRL), or low (n = 12; 21 ± 4 ng/ mL PRL). Data were analyzed with Pearson correlations, and repeated measures ANOVA with month and prolactin category (PRLCAT) as main effects. Concentrations of PRL were correlated (r &amp;gt; 0.53; P &amp;lt; 0.0001) over the three months, and May PRL concentrations were correlated (r &amp;gt; 0.29; P &amp;lt; 0.02) with cow body weights in May, June, and July. Cows in the low PRLCAT had lower (P &amp;lt; 0.01) concentrations of PRL in all three months. Hair coat score decreased (P &amp;lt; 0.0001) each month (4.3, 2.7, and 1.3; respectively, May, June, July), and was higher (P &amp;lt; 0.05) for cows with low PRLCAT (3.3 vs. 2.7 and 2.4 for low, medium, and high, respectively). Cow body weight increased (P &amp;lt; 0.0001) from May to July. Cows in the low PRLCAT had lower (P &amp;lt; 0.05) body weights than medium and high PRLCAT cows (484 vs. 555, and 575 kg; respectively). Concentrations of PRL in May could be useful in identifying cattle with slick hair coats and heavier body weights.

MON-459 ONO-5788, a Novel Oral Small Molecule Somatostatin Receptor Type-2 (SST2) Agonist, Attenuates GH Hypersecretion in Human GH-Secreting, Pituitary Adenoma-Derived Cells

Somatostatin receptor ligands (SRL) and GHR antagonists are used for persistent or recurrent acromegaly following noncurative surgery and as primary therapy for patients unsuitable for surgery. We tested in vitro action of a novel oral SRL compound ONO-5788 and its active metabolite (ONO-ST1-641) which signals via SST2. With IRB approval and informed consent, 12 human somatotroph adenomas, obtained at transsphenoidal resection were cultured. In the 1st cohort, 8 somatotroph adenomas were treated with ONO-ST1-641 (0, 100, 1000 nM) and octreotide (OCT, 100 nM) for 24 h, and media collected at 2, 6, and 24 h respectively to assess GH and PRL concentrations by ELISA. Cells harvested at 24 h were used to measure mRNA levels of SST2 and SST5, hormone genes and cell cycle genes CDKN1A, CDKN1B by qPCR. Three of 8 tumors (38%) responded to ONO-ST1-641 and OCT as early as 2 and 6 h. GH was significantly reduced by OCT (18% to 58% reduction, P<0.05) and similarly attenuated by ONO-ST1-641 (28 to 59% reduction, P<0.05). GH secretion in 6 of 8 tumors (75%) was decreased at 24 h, showing reduction by OCT and ONO-ST1-641 by up to 48% (P<0.01) and 50% (P<0.01), respectively. PRL levels were undetectable, very low or unchanged by treatments. Related compound ONO-5788 showed similar responses. SST2 and SST5 expression was unchanged during treatments in the 6/8 responders as assessed by TaqMan qPCR using HPRT1 and GAPDH as controls. Neither was GH, PRL, CGA, CDKN1A and CDKN1B mRNA expression altered by ONO-ST1-641 or OCT for 24 h, as assessed by SYBR qPCR using RPL13A, GAPDH and 18S as controls, suggesting that ONO-ST1-641 did not affect these hormone genes and cell cycle regulator mRNA levels. In the 2nd cohort, pretreatment baseline SST2 and SST5 expression were assessed in 4 cultured tumors treated with ONO-ST1-641 (0, 100, 1000 nM) or OCT (100 nM) for 6 h. Untreated tumor cell mRNA was extracted at baseline to assess SST2 and SST5 expression and GH and PRL measured at 6 h. Two of 4 tumors were unresponsive to both ONO-ST1-641 and OCT, 1 showed mild GH reduction by ONO-ST1-641 (15%) but not by OCT. Notably, 1 specimen expressing highly abundant baseline SST2 exhibited marked GH suppression by ONO-ST1-641 and OCT at 6 h (63 and 62%, respectively, P<0.01). High baseline SST2 expression further validated by Western blot and confocal immunofluorescence, imply that SST receptor expression associates with ONO-ST1-641 responsiveness. Available SRLs and GHR antagonists are parenteral, requiring lifelong injection, with variable and suboptimal efficacy, necessitating development of novel oral small molecule drugs for acromegaly. Our study provides preclinical evidence that ONO-5788 and its active metabolite attenuate GH hypersecretion in primary somatotroph adenoma cells cultures, suggesting the potential application of ONO-5788 for acromegaly patients.

OR24-3 Persistence of Progenitor Cell Markers Following the Selective Ablation of Musashi in Somatotropes

Metabolic and reproductive demands are met and coordinated through the complex control of hormone synthesis and secretion exerted by the anterior pituitary. While pituitary cells are known to possess remarkable plasticity to change their cell fate and alter hormone production in response to ever changing environmental cues, the underlying molecular control of this plasticity has not been established. Our lab has previously introduced the Musashi (MSI) family of RNA binding proteins as important players in control of pituitary hormone levels. Musashi typically governs stem cell fate and promotes self-renewal by repressing translation of target mRNAs needed for differentiation. However, we found that MSI1 is expressed in most differentiated cells of the adult pituitary and can specifically bind to the 3’ UTRs of Prl, Tsh, and Pou1f1 and exert translational control in reporter assays. Confirmation of the requirement for MSI was demonstrated through in vivo analyses where MSI1 and MSI2 were selectively ablated in somatotropes. The mutant animals were subfertile. The mutant males showed reduced serum and pituitary content of LH and FSH, and significant decreases in serum GH and PRL despite 2-fold increases in pituitary protein content of PRL and GH. To further assess the role and downstream pathways regulated by MSI in the pituitary, we collected somatotrope MSI-null pituitaries from males and females for qPCR analysis of common somatotrope target genes. In correlation with our previous findings described above (low serum GH and high pituitary GH content), we found that GHRHR mRNA levels were reduced by 2-fold in male mutants. RNA-seq analysis followed by qPCR validation shows that Prop1 mRNA was significantly increased in male mutants, with no significant change in Pou1f1 mRNA. These data suggest that MSI may be involved in the regulation of progenitor cells giving rise to the somatotrope lineage and that MSI ablation may have caused retention of these progenitors and/or a failure to fully differentiate somatotropes. Our studies of MSI-null somatotrope function support this interpretation because the mutant somatotropes clearly stored GH proteins, but could not secrete them, as demonstrated by the low serum GH values, and the 50% reduction in GHRHR mRNA. RNA-seq evaluation of males revealed a change in the expression of 720 genes between controls and mutants (FDR <0.05). When we examined female MSI-null somatotrope animals, a much smaller cohort of genes showed a change in expression (153 genes, FDR <0.05). Interestingly, 38 genes were altered in both mutant males and females suggesting shared regulation by MSI. Further characterization of the NGS datasets will elucidate additional downstream targets and effector pathways of MSI-dependent control of anterior pituitary cell differentiation and function.

Impact of slick hair trait on physiological and reproductive performance in beef heifers consuming ergot alkaloids from endophyte-infected tall fescue1.

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue. The objective of this study was to evaluate the impact of the slick hair trait on physiological and reproductive parameters in heifers experiencing fescue toxicosis. Angus × Senepol heifers (n = 31) were blocked by weight (393.5 ± 17.3 kg) and phenotype relative to hair coat at birth, and randomly fed novel endophyte fescue (EN) or endophyte-infected fescue (EI) haylage in a total mixed ration for 91 d. Weekly measurements were collected to monitor heifer growth and response during ergot alkaloids exposure. Following 28 d of treatment, estrus was synchronized and heifers were inseminated. Ovary mapping and AI pregnancy rate were examined via transrectal ultrasonography. Blood samples were taken for genotyping: slick (S) or wildtype (W). Data were analyzed using repeated measures in PROC MIXED of SAS including fescue treatment (EN vs. EI), genotype (S vs. W), and sample collection time as main effects. Body condition scores were decreased for W heifers compared with S heifers (5.48 vs. 5.66, respectively; P < 0.0001). Surface temperature was greater for EI-W heifers (37.2 °C) compared with other groups (36.4, 36.6, 36.7 °C for EN-S, EN-W, EI-S, respectively; P < 0.05). Serum PRL concentrations were reduced for EI heifers compared with EN heifers (133.5 vs. 163.1 ng/mL, respectively; P < 0.05). The average number of 2 to 4 mm follicles were greater in EI-W heifers (13.8 follicles) compared with other groups (12.2, 10.6, and 11.1 for EN-S, EN-W, and EI-S, respectively; P < 0.0001). However, the average number of preovulatory follicles (≥9 mm) were reduced in EI-W heifers (0.52 follicles) compared with other heifer groups (0.94, 0.88, and 0.85 ± 0.04 for EN-S, EN-W, and EI-S, respectively; P < 0.05). Ovulatory follicle size was smaller in EI-W heifers compared with EN-W heifers (9.14 vs. 11.57 mm, respectively; P = 0.05). Corpus luteum area was reduced in EI-W heifers (235.1 mm2) compared with other heifer groups (297.2, 272.7, and 276.8 mm2 for EN-S, EN-W, and EI-S, respectively; P < 0.05). Concentrations of P4 were greater for EN heifers compared with EI heifers (2.7 vs. 1.8 ng/mL, respectively; P < 0.05). Pregnancy was not established in EI-W heifers (0%) compared with other heifer groups (37.5%, 57.1%, and 62.5% for EN-S, EN-W, and EI-S, respectively; P < 0.05). Overall, the slick hair mutation appears to aid in offsetting the physiological symptoms associated with fescue toxicosis and helps to improve reproductive performance.

Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice.

Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance.

Giant Prolactinoma in Men: Clinical Features and Therapeutic Outcomes.

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3-211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3-222 months; NS) served as a control group. More than half (56.5%) of the gPRLoma patients were younger than 40 years at diagnosis. Visual disturbances were significantly more common in gPRLoma than in non-gPRLoma patients (65.2 vs. 25.6%; p=0.004). Prevalence of hypopituitarism was similar in both groups of patients (73.9% vs. 80.9%; gPRLoma vs non-gPRLoma; NS). Serum PRL concentrations were significantly higher in gPRLoma than in non-gPRLoma patients [median (IR), 3978 ng/ml (1179-9012) vs. 907 ng/ml (428-3119); p<0.001]. Maximum tumor diameter in gPRLomas was 4.8±0.8 cm and 2.4±0.7 cm in non-gPRLoma (p<0.001). All patients were treated with dopamine agonists (DA). Twelve (52.2%) gPRLoma patients and 32 (73.8%) non-gPRLoma patients were treated with DA as monotherapy (p=0.045). Surgery was used in 12 (52.2%) gPRLoma patients and in 12 (28.6%) non-gPRLoma patients (p=0.054). Lastly, radiotherapy was used in 5 (21.7%) gPRLoma patients and in 6 (14.2%) non-gPRLoma patients (NS). At last visit, PRL was similar in both groups of patients [16 ng/ml (4-30) vs. 11 ng/ml (4-25); gPRLomas vs. non-gPRLomas; ns] and tumor size decreased significantly (p<0.001) in both groups of patients. Clinical cure (maintained normoprolactinemia without therapy for>1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients.

Giant Prolactinomas: Outcomes of Multimodal Treatments for 42 Cases with Long-Term Follow-Up.

Giant prolactinomas represent a rare entity of pituitary tumors so that the management of these patients is still a prevalent challenge at present. Paying special attention to the treatment strategy and outcomes, we presented a large series of 42 cases looking forward to share our understanding and experience in management of these patients. Male patients accounted for 71.4% of this series and were relatively younger (35.70±2.42 vs. 52.00±3.55 years, p=0.0011) and harbored bigger tumors (14.57 vs. 7.74 cm3, p=0.0179) compared to females. Almost all of these tumors showed suprasellar extension (97.6%) and cavernous sinus invasion (92.9%). Dopamine agonist represented an efficient method to control PRL concentrations (98.8%) and reduce tumor burdens (81.2 %). PRL normalization was detected in 13 out of the 27 patients initially treated with bromocriptine (BRC) whereas none of the 14 patients with first-line operation gained a normalization of PRL concentration after surgery. Although there was no reliable predictor of tumor response, First PRL reduction was a predictive criterion for the nadir PRL level during the long-time period of follow-up for first-line bromocriptine treatment. In conclusion, patients with giant prolactinomas did not gain more benefits from initial surgery. Dopamine agonist (BRC) should be first-line treatment for giant prolactinomas whereas operation merely served as a remedy for acute compression symptoms and dopamine agonist resistance. Consecutive monitoring of serum PRL levels in the early stage of initial BRC treatment is useful for evaluation of therapeutic effect and further therapeutic decision.

Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels.

The neurohypophyseal hormone oxytocin (Oxt) has been shown to stimulate prolactin (Prl) synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr), namely isotocin (Ist) receptor 1 (Istr1) and 2 (Istr2), were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh) cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

Serum sex hormones concentrations in young women in the early period after successful kidney transplantation.

Hormonal disorders are frequently present in hemodialysed patients with chronic kidney disease (CKD). In women with CKD sex hormones abnormalities may lead to irregular, often anovulatory cycles, sexual dysfunction and infertility. Kidney transplantation done in young women tends to ameliorate most of the aforementioned disorders and improve fertility. The aim of this study was to assess the changes of serum sex hormones concentration in young women before, and after the first 6 months after successful KTx Material and methods: Fourteen chronic hemodialysis women with CKD undergoing kidney transplantation and 46 apparently healthy women in similar age (control group) were enrolled into the study. In all women serum concentration of: FSH, LH, PRL and estradiol determined. Measurements in the transplanted group were done four times: immediately before surgery, in the 14th - and 30th - day and 6 months after the transplantation. The results are presented as means and 95% CI. All of the women that have finished the study presented an excellent function of the transplanted kidney - mean serum creatinine concentration was 92.54 (74.85 - 110.23) µmol/l. After successful KTx a significant decrease in the serum concentrations of FSH and LH was observed. Decrease of serum PRL concentration after KTx did not reach statistical significance in the multiple comparisons analyses, but returned to the values observed in healthy controls. KTx did not significantly influence serum estradiol concentration. Successful kidney transplantation leads to the normalization of serum concentrations of hormones linked to fertility disorders in women with chronic kidney disease. < p > < /p >.

TSH and PRL, side-effect markers in aripiprazole treatment: adjunctive aripiprazole-induced thyrotropin oversuppression in a young man with schizophrenia

A 26-year-old Japanese man was admitted to our unit with exacerbated paranoid schizophrenia. Prior to his admission, daily administration of olanzapine had been sufficient to maintain a partial remission of...

Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31–3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206–0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983–0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951–0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium.

Assessment of Thyroid Functions Test among Hyperprolactinemic Sudanese Infertile Females

Background: Hyperprolactinemia is the most prevalent endocrine disorder in hypothalamic- pituitary axis especially among reproductive age women. This cross section study was conducted to assess thyroid function among infertile Sudanese female with hyperprolactinemia. Methods: One hundred infertile Sudanese females with hyperprolactinemia were chosen for this study and 50 infertile Sudanese females with normal prolactin level were used as controls. All individuals were within the same age group (16-42). Prolactin, LH, FSH, TSH, T4 and T3 were measured in both group by Radioimmunoassay. Results: 17% of hyperprolactinemic patients were found to be with hypothyroid; interestingly no case was reported to have hypothyroidism or other thyroid dysfunction in the control group. The concentrations of serum PRL and TSH was significantly higher than in the control group while the level of LH and FSH were found to be significantly lower than in the control positive association was found between PRL and TSH among hyperprolactinemic patients. Conclusions: This study was found an association between hyperprolactinemia and hypothyroidism. The relatively high occurrence of hypothyroidism among hyperprolactemic infertile females emphasizes the importance of estimating both serum prolactin and TSH in infertility.

Brain prolactin is involved in stress-induced REM sleep rebound

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound.

The genetic background of climacteric symptoms in women during menopause

The subject of the study is the evaluation of the correlation between the polymorphism of candidate genes in the etiology of depression and the occurrence of the symptoms of the climacteric syndrome in women during menopause. The group subjected to the study comprised of 203 women aged between 42-65 years: 71 of them still menstruated (premenopausal group) and 132 at least one year after the last period (postmenopausal group), admitted to the Department of Gynecological Endocrinology at the University of Medical Sciences in Poznan with symptoms of the climacteric syndrome. All the examined women were evaluated according to the degree of severity of the climacteric syndrome symptoms using the Kupperman index and the concentration of FSH, LH hormones, 17&#x03B2;-estradiol, PRL, total testosterone, and DHEAS in peripheral blood serum. Among the candidate genes in the aetiology of depression the following were selected for the research: the serotonergic system receptor genes: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, and MAO-A; the genes of noradrenergic and dopaminergic systems (COMT, NET), the genes of the GABAergic (GABRB1) system, a gene of the estrogen receptor (ESR1), and the genes of the enzymes crucial in the methyl cycle (MTHRF, MTR, and MTHFD1). With regards to the correlation between the examined polymorphisms and the occurrence of the symptoms of the climacteric syndrome, the associations analysis indicated a connection between GABRB1.TaqI polymorphism and the occurrence of vertigo in premenopausal women (0.0198; after correction: 0.0497 CC to CA). The correlation was also found regarding the examined polymorphisms and the concentration of the examined hormones in blood serum: TPH1.MaeI polymorphism and the LH concentration in the postmenopausal group (0.004; after correction: 0.014 CC to CA), NET.Eco147I polymorphism, and the 17&#x03B2;-estradiol concentration in the postmenopausal group (0.0208; after correction: 0.048 GG to GA) and HTR2AMspI polymorphism and PRL concentration in all examined women (0.03; after correction: 0.038 TT to CT).

Prolactin receptor and osteogenic induction of prolactin in human periodontal ligament fibroblasts.

Prolactin is an important hormone involved in the interaction between maternal, extraembryonic, and fetal tissues that remains in high levels during the entire duration of pregnancy. Although many systemic alterations occur during pregnancy, such as hormonal changes, that are known to be associated with periodontitis and tooth loss, PRL function in human periodontal ligament fibroblasts (HPDLF) had never been studied. Herein, we investigated the role of PRL in the regulation of HPDLF proliferation and differentiation. HPDLF were cultured in differentiating medium with various concentrations of PRL. The present study demonstrated that HPDLF and primary human PDL cells that were extracted for orthodontic purpose expressed both short and long isoforms of PRLR mRNA and its proteins. An incubation with of high concentration of PRL (600 and 1,000 ng/mL) modestly decreased the HPDLF number. In contrast, PRL at a non-reproductive level (10 ng/mL) and pregnant level (100 ng/mL) significantly upregulated the markers of osteogenesis, such as RUNX2, BMP2, and POSTN, but not SOX9. Mineral nodule formation was induced, whereas proteoglycan accumulation was reduced by PRL suggesting that HPDLF were undergoing differentiation into preosteoblastic cells. In conclusion, the presence of hPRLR in human PDL together with PRL-induced upregulation of osteogenic markers strongly suggested a direct regulatory role of PRL in PDL and periodontal tissue development.

125 CHANGES IN INTRAFOLLICULAR CONCENTRATIONS OF FREE INSULIN-LIKE GROWTH FACTOR-1, ACTIVIN-A, INHIBIN-A, VASCULAR ENDOTHELIAL GROWTH FACTOR, ESTRADIOL, AND PRL BEFORE OVULATION IN MARES

Intrafollicular factors and hormones during the process of follicle deviation have been studied extensively in mares. However, knowledge is still lacking concerning the dominance and preovulatory (postdeviation) phases of the oestrous cycle. Furthermore, information about intrafollicular growth factors and hormones during postdeviation growth is critical for understanding the ovulatory and post-ovulatory physiological mechanisms that have important in vivo and in vitro applications, such as oocyte maturation, ovulation, and embryo development and survival. Changes in intrafollicular growth factors and hormones were evaluated in vivo in postdeviation and impending ovulation follicles. Hormone and growth factor concentrations were determined by ELISA or RIA. Mares (n = 30) were randomly assigned to 5 experimental groups based on target diameters of 25, 30, 35, 40 mm, and impending signs of ovulation. Data were analysed by one-way ANOVA, paired-test, and Pearson correlation. Data belonging to 2 or more proximal diameter groups that were not different were combined and regrouped for each factor separately. When the data were regrouped (all results shown below), follicular fluid-free insulin-like growth factor-1 was higher (P &lt; 0.003) in 35-mm follicles than in the 25- to 30-mm and 40-mm impending ovulation follicle groups. The 25- to 30-mm follicle group had the lowest insulin-like growth factor-1 concentration. However, concentrations of insulin-like growth factor binding protein-2 in follicular fluid did not differ (P &gt; 0.05) among groups. Additionally, follicular fluid activin-A tended (P &lt; 0.06) to be higher in impending ovulation follicles when compared to the 25- to 40-mm follicle group. Concentrations of intrafollicular oestradiol were higher (P &lt; 0.0001) in 40-mm impending ovulation follicles than in the other follicle groups. Follicular fluid concentrations of inhibin-A and vascular endothelial growth factor were lower (P &lt; 0.02–0.002) in the 40-mm impending ovulation follicle group when compared to the 25- to 35-mm follicle group. Systemic and intrafollicular PRL were lower (P &lt; 0.05) in the impending ovulation group when compared to the 25- to 40-mm follicle group. PRL concentrations were higher (P &lt; 0.05) in the follicular fluid than in the plasma. The novel findings of this study, a decrease in intrafollicular free insulin-like growth factor-1, inhibin-A, vascular endothelial growth factor, and PRL during the final stages of follicular growth, document for the first time the occurrence of dynamic changes among intrafollicular factors and hormones during the stages of follicle dominance and as ovulation approaches. Overall, the elucidation of the role of follicular fluid factors and hormones and their interactions need to be studied further to allow a better understanding of the ovulatory process in mares. This knowledge will potentially assist in obtaining better outcomes during the use of assisted reproductive technologies and will also help to understand mechanisms of ovulatory dysfunctions in mares and perhaps in other species.

Seasonal Expression of Prolactin Receptor in the Scented Gland of Male Muskrat (Ondatra zibethicus).

Prolactin (PRL) has numerous actions in mammalian biological systems including mammary development and biological processes. The aim of this study was to investigate the seasonal changes of prolactin receptor (PRLR) expression in the scented gland of muskrat during the breeding and nonbreeding seasons. Histologically, glandular cells, interstitial cells and excretory tubules were identified in the scented glands in both seasons, whereas epithelial cells were sparse in the nonbreeding season. PRLR was observed in glandular cells of scented glands during the breeding and nonbreeding seasons with stronger immunostaining during the breeding season. Consistent with the immunohistochemical results, both the mean of protein and mRNA levels of PRLR were higher in the scented glands of the breeding season, and relatively lower level in the nonbreeding season. In addition, differential seasonal changes were also detected in the expression profile of microRNAs (miRNAs) in the scented gland of muskrat. Besides, plasma PRL concentration was remarkably higher in the breeding season than that in the nonbreeding season. These results suggested that muskrat scented gland was the direct target organ of PRL, and stronger expression of PRLR in scented glands during the breeding season indicated that PRL may directly regulate scented glandular function of the muskrats.

The Role of Melatonin and Bromocriptine in the Regulation of Prolactin Secretion in Animals – A Review

Abstract Changes in the concentration of melatonin and prolactin are associated with response to day length. The factors that stimulate the release of PRL include, among others, TRH, VIP, endorphins, oestrogen, and adrenaline. PRL secretion inhibitors include DA, GABA, progesterone and bromocriptine (exogenous compound), used in the treatment of hyperprolactinemia D2 receptor agonist. The biological activity of this compound is to stimulate dopamine D2 receptors in the pituitary, which inhibits PRL secretion via the tuberoinfundibular pathway (Fitzgerald and Dinan, 2008). In sheep treated with bromocriptine there is a decrease in PRL concentration and an increase in the sensitivity of cells producing LH to GnRH, but there is no disturbance in the course of the estrous cycle. Rams show decreased libido and changes in sexual behaviour. The administration of bromocriptine throughout the period of sexual activity and the period of rearing offspring affects maternal instinct, which involves the inhibition of PRL secretion. It is not clarified whether the effect of bromocriptine on sexual behaviour is associated with its direct impact on behavioural centres in the brain, or indirectly through the regulation of PRL secretion. However, the seasonal variations in the effects of bromocriptine on sexual behaviour can strengthen the hypothesis that the effect of bromocriptine on sexual development behaviour is associated with changes in the intensity of PRL secretion rather than by the inhibition of behavioural bromocriptine brain centres. The process of regulation of prolactin secretion by bromocriptine requires further examination.

Atrazine triggers developmental abnormality of ovary and oviduct in quails (Coturnix Coturnix coturnix) via disruption of hypothalamo-pituitary-ovarian axis

There has been a gradual increase in production and consumption of atrazine (ATR) in agriculture to meet the population rising demands. Female reproduction is necessary for growth and maintenance of population. However, ATR impact on females and particularly ovarian developmental toxicity is less clear. The aim of this study was to define the pathways by which ATR exerted toxic effects on ovarian development of ovary and hypothalamo-pituitary-ovarian (HPO) axis. Female quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50, 250 and 500 mg ATR/kg/d for 45 days. ATR had no effect on mortality but depressed feed intake and growth and influenced the biochemical parameters. Notably, the arrested development of ovaries and oviducts were observed in ATR-exposed quails. The circulating concentrations of E2, P, LH and PRL were unregulated and FSH and T was downregulated in ATR-treated quails. The mRNA expression of GnRH in hypothalamo and LH in pituitary and FSH in ovary was downregulated significantly by ATR exposure and FSH and PRL in pituitary were upregulated. ATR exposure upregulated the level of P450scc, P450arom, 3β-HSD and 17β-HSD in ovary and downregulated ERβ expression in female quails. However, ATR did not change ERα expression in ovary. This study provides new insights regarding female productive toxicology of ATR exposure. Ovary and oviduct in sexually maturing females were target organs of ATR-induced developmental toxicity. We propose that ATR-induced developmental abnormality of ovary and oviduct is associated with disruption of gonadal hormone balance and HPO axis in female quails.