Rat Prolactin Research Articles

Comparative Study of Lactogenic Effect and Milk Mutritional Density of Oral Galactagogues in Female Rabbit.

Hypogalactia and agalactia in lactating mothers are the major causes of child malnutrition, mortality, morbidity, and overall ill health. The development of such treatments requires a well-designed preclinical study with suitable laboratory animals, which needs to be improved. Thus, a suitably designed study with a laboratory animal to analyse galactagogue activity, along with an assessment of the quality and quantity of milk, is required. This study aimed to evaluate the potential of rabbits as an animal model for studying lactogenic activity. The structural homology of prolactin, prolactin, and prolactin in humans, rabbits, and rats was studied using BLAST and PyMol to assess similarity in the lactogenic system. Daily and cumulative milk production and pre-treatment (control) and post-treatment (three drugs) in rabbits were recorded and evaluated by analysing protein, fat, lactose, solid non-fat, and ash values. All parameters were recorded on the 0th day and at the end of weeks 1, 2, and 3. Mammary gland histopathology was performed to evaluate the effects on mammary glands. Homology studies revealed that the sequences of the human and rabbit prolactin genes, receptors, and hormones had a high similarity index. Treatment with Domperidone, Metoclopramide, and Shatavari significantly enhanced milk production by enhancing prolactin secretion; only Shatavari increased milk nutrition. Enlargement of the tubuloalveolar ducts of the mammary glands was observed. Our findings suggest that rabbits are robust, reproducible, ethically superior, and preclinically relevant animals for assessing lactogenic activity.

Cuiru Keli Improves Postpartum Hypogalactia in Rats Through Secreted Frizzled-Related Protein 2-Wnt/β-catenin Signaling Pathway

Based on the secreted frizzled-related protein 2 (SFRP2)-Wnt/β-catenin signaling pathway, this study explored the effect and mechanism of Cuiru Keli (CRKL) in the treatment of postpartum hypogalactia. A rat model of postpartum hypogalactia was established by gavaging 2 mL of 1.6 mg/mL bromocriptine mesylate to female rats on the third day after delivery. Female rats with a delivery time difference of less than 48 hours were selected and randomly assigned to 7 groups, including a normal group (without any modeling or medication), a model group, a CRKL low-dose group of model group model rats receiving CRKL at the dose of 3 g/kg, a CRKL medium-dose group of model rats receiving CRKL at the dose of 6 g/kg, a CRKL high-dose group of model rats receiving CRKL at the dose of 9 g/kg, a positive drug group of model rats receiving domperidone at the dose of 3 mg/kg, and a negative control (NC) group of model rats receiving normal saline. Each group contained 6 rats. Except for the normal and model groups, the remaining 5 groups were continuously administered with the respective intervention drugs at the specified doses by gavage once a day for 10 days. Changes in the total litter mass of the offspring in the 7 groups within 10 days were measured, and HE staining was performed to identify pathological changes in the mammary tissue (MT). Six groups of rats (excluding the positive control group) were used to observe the pathological changes of eosinophils in pituitary tissue. ELISA was performed to determine the content of prolactin (PRL) in serum, immunohistochemical staining was used to determine the expression of prolactin receptor (PRLR) in MT, and RT-qPCR was used to determine the mRNA expression of genes related to lactation in MT. Network pharmacology and molecular docking were used to study the therapeutic effect and mechanism of CRKL on postpartum hypogalactia, particularly whether it acted through the SFRP2-Wnt/β-catenin signaling pathway. The mechanism of CRKL treatment was further validated by detecting mRNA (RT-qPCR) and protein expression (Western blot) of related pathway genes. Cell experiments were conducted using primary culture rat mammary epithelial cells (RMEC) from rat MT. RMEC were divided into four groups, including a normal group (primary culture RMEC, untreated), SFRP2 overexpression group (primary cultured RMEC treated with SFRP2 overexpression vector), SFRP2 overexpression+CRKL group (receiving treatment for SFRP2 overexpression group plus 10% drug-containing serum), and negative control group (primary culture RMEC treated with empty vector). The effect of CRKL on the expression of lactation-related genes FASN, CSN2, and GLUT1 mRNA after SFRP2 overexpression was detected by RT-qPCR. In this study, CRKL was administered at a dose of 3 g/kg in the CRKL low-dose group, 6 g/kg in the medium-dose group, and 9 g/kg in the high-dose group (P<0.05 or P<0.01). Compared with the model group, CRKL at all doses significantly increased the total litter weight gain of the offsprings within 10 days (P<0.05 or P<0.01), and effectively increased lactation (P<0.01), the area of mammary lobules, and the size and filling of acinar cavities. CRKL at all doses also increased the number of eosinophils that secreted PRL in the pituitary gland of the postpartum hypogalactia rat model, and increased the content of PRL in the serum (P<0.05 or P<0.01). CRKL promoted the secretion and expression of PRL in postpartum hypogalactic model rats. In addition, it significantly promoted the expression of genes related to milk fat, milk protein, and lactose synthesis in MT (P<0.05 or P<0.01). Network pharmacology predicted that the Wnt signaling pathway might be a key pathway for CRKL in treating postpartum hypogalactia. The molecular docking results showed that related chemical components in CRKL had good binding ability with CCND1 and SFRP2. Compared with the model group, CRKL at all doses inhibited the expression of SFRP2 gene in vivo (P<0.01) and activated the mRNA and protein expression of CCND1 and c-Myc in the Wnt/β-catenin signaling pathway in MT (P<0.05 or P<0.01). Cell experiments showed that, compared to the normal group, SFRP2 overexpression reduced the mRNA expression of milk synthesis-related genes FASN, CSN2, and GLUT1 in RMEC (P<0.01). The CCK8 results indicated that 10% of the drug-containing serum was the effective concentration administered to cells (P<0.01). After administering drug-containing serum, the expression of the lactation-related genes FASN, CSN2, and GLUT1 were up-regulated (compared with the SFRP2 overexpression group, P<0.01). CRKL alleviates postpartum hypogalactia through the SFRP2-Wnt/β-catenin signaling pathway. SFRP2 might be a potential new target for the diagnosis and treatment of postpartum hypogalactia. This reveals a new mechanism of CRKL in treating postpartum hypogalactia and promotes its clinical application.

Freeze-dried powder of daylily bud improves bromocriptine-induced lactation disorder in rats via JAK2/STAT5 pathway

Ethnopharmacological relevanceMilk deficiency is a prevalent problem in the world. Daylily (Hemerocallis citrina Borani), called the Chinese mother flower, is a traditional vegetable and is believed to possess a galactagogue effect in China. Flavonoids and phenols are considered as the active ingredients of daylily to promote lactation and improve depression. Aim of the studyThe aim of this study was to investigate the prolactin effects of freeze-dried powder of flower buds of H. citrina Baroni in rat and its action mechanisms. Materials and methodsThe chemical constituents of flower buds of H. citrina Baroni treated by different drying techniques were analyzed by ultrahigh pressure liquid chromatography-mass spectrometry. Sprague-Dawley (SD) rat model induced by bromocriptine was used to evaluate the effect of freeze-dried powder of daylily buds on promoting lactation. Network pharmacology method, ELISA, qPCR, and Western blot were used to clarify the action mechanisms. ResultsWe detected 657 compounds in daylily buds. The relative contents of total flavonoids and phenols in freeze-dried samples were higher than those in dried ones. Bromocriptine, as a dopamine receptor agonist, can significantly inhibit prolactin in rats. Daylily buds can restore the levels of prolactin, progesterone and estradiol depressed by bromocriptine, effectively improve the milk production of the rat, and promote the repair of rat mammary gland tissue. We analyzed the relationship between the chemical components of daylily buds and the genes related to lactation with network pharmacology method, revealing that flavonoids and phenols may be the active components that promoted milk production via JAK2/STAT5 pathway, which was confirmed by the results of qPCR and Western blot. Daylily buds can increase the mRNA expression of PRLR, CSN2, LALBA and FASN and the protein expression of PRLR, JAK2 and STAT5. ConclusionDaylily buds can improve the insufficient lactation of rats induced by bromocriptine through PRLR/JAK2/STAT5 pathway, and the freeze-dried processing method may better retain the active components of flavonoids and phenols that promote milk in daylily.

Effect of dexamethasone administration on gonadal-fertility functions in female albino rats.

dexamethasone is misused for skin whitening with broad effects on steroidogenesis and ovarian functions. Here in we investigated the impact of dexamethasone administration on gonadotropin Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), prolactin, and ovarian tissues in albino rats. in the experimental study, 36 female albino rats weighting (140-162 g) were divided into three groups: control, normal dose received dexamethasone (8.3 μg/kg/day) and high dose (24.9 μg/kg/day), for 30 and 60 days. follicle stimulating hormone, luteinizing hormone, and prolactin (PRL) were measured. Histological ovarian sections were examined. luteinizing hormone, follicle stimulating hormone and prolactin significantly increased (p-value < 0.05) following dexamethasone treatment compared to control. The ovary sections showed degenerative tissue with necrosis of the Graafian follicles, stromal fibrosis, and vacuolation of the interstitial cells. the study concludes that dexamethasone administration has a potentially adverse effect on gonadotropin, prolactin, and ovarian follicle cells in female albino rats.

TRH Regulates the Synthesis and Secretion of Prolactin in Rats with Adenohypophysis through the Differential Expression of miR-126a-5p.

Prolactin (PRL) is an important hormone that is secreted by the pituitary gland and plays an important role in the growth, development and reproduction of organisms. Thyrotropin-releasing hormone (TRH) is a common prolactin-releasing factor that regulates the synthesis and secretion of prolactin. In recent studies, microRNAs (miRNAs) have been found to play a key role in the regulation of pituitary hormones. However, there is a lack of systematic studies on the regulatory role that TRH plays on the pituitary transcriptome, and the role of miRNAs in the regulation of PRL synthesis and secretion by TRH lacks experimental evidence. In this study, we first investigated the changes in PRL synthesis and secretion in the rat pituitary gland after TRH administration. The results of transcriptomic analysis after TRH treatment showed that 102 genes, including those that encode Nppc, Fgf1, PRL, Cd63, Npw, and Il23a, were upregulated, and 488 genes, including those that encode Lats1, Cacna2d1, Top2a, and Tfap2a, were downregulated. These genes are all involved in the regulation of prolactin expression. The gene expression of miR-126a-5p, which regulates the level of PRL in the pituitary gland, was screened by analysis prediction software and by a dual luciferase reporter system. The data presented in this study demonstrate that TRH can regulate prolactin synthesis and secretion through miR-126a-5p, thereby improving our understanding of the molecular mechanism of TRH-mediated PRL secretion and providing a theoretical basis for the role of miRNAs in regulating the secretion of pituitary hormones.

Cultivation Techniques of &lt;i&gt;Secamone afzelii&lt;/i&gt; and Effect of its Ashes on Rats Prolactin Contains

Cultivation Techniques of &lt;i&gt;Secamone afzelii&lt;/i&gt; and Effect of its Ashes on Rats Prolactin Contains

Docosahexaenoic Acid Prevents SiNPs Induced Alterations in Male Reproductive Hormones in Rats

Silica nanoparticles (SiNPs) are found to be toxic during excessive exposure for both human and animals (Fan et al., (2006). The main routes of exposure are air, drinking water and other environmental factors (Leung et al., 2012). It is reported that SiNPs decreased the sperm number and sperm motility rate, sperm malformation and apoptosis in the testicle spermatogenic cells in rats (Ying et al., 2014). Aim of the present study is to evaluate deterioration induced by SiNPs in male reproductive hormones. In the present study, 40 and 80 mg SiNPs were exposed to rats for 60 days. At the end of the exposure period serum were removed from the blood for the investigation of reproductive hormones such as Folicle stimulating Hormones (FSH), Leutinizing Hormones (LH), Testosterone (TT) and Prolactin (PROL) in both control and experimental rats. In the present study it was found that LH, FSH, Testosterone and Prolactin values significantly alters SiNPs exposed groups when compared with control groups. We also found that epididymal sperm count was decreased significantly in the experimental groups. On the basis of results it may be concluded that the interperitoneal injection of SiNPs alters the male reproductive hormones, which further deteriorate the spermatogenesis.

Postpartum Fatigue and Inhibited Lactation

Background:Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives:This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats.Methods:Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results:The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion:Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.

Detection of Active Compounds in the Water Extract of Foeniculum Vulgare L. and Its Effects on Serum Estrogen and Prolactin Levels in Female Albino Rats

The present study was designed to estimate the active ingredients in the aqueous extract of fennel Foeniculum vulgare L. fruits and test the effects of different concentrations of the extract on serum estrogen and prolactin levels in female rats. The work was conducted to prepare the aqueous extract in the laboratory, while the secondary active substances in the extract were estimated using High-Performance Liquid Chromatography (HPLC) technology. The experiments were conducted in the animal house of the College of Science, Tikrit university,on a total of 12 adult albino virgin female rats divided into four groups, each having three rats.The aqueous extract of the fruit plant was administrated orally to animals at three concentrations (50%, 75%, and 100%) per day for 45 days. The fourth group was the control group that was left without treatment. Blood samples were obtained from the corner of the eye with a capillary tube and the serum was extracted to determine the hormone levels. The results showed that the aqueous extract of fennel fruits contains eleven active secondary metabolites, namely Eucalyptol, Terpinene, Anisole, Camphor, Anethole, Anisaldehyde, Apiole, a-pinene, Estragole, Fenchone, and Limonene, which seemed to played a role in regulating the levels of prolactin and estrogen hormones in rats treated with the extract. The results showed a direct relationship between the concentration of the fruit extract given to the animals and their serum levels of estrogen and prolactin. Increases in the levels of estrogen (44.56 ± 0.90 ng/ml) and prolactin (134.66 ± 0.80 ng/ml) were recorded using the concentration of 100% of the watery extract of Foeniculum vulgare L., as compared to the control group (126.33 ± 1.18; 6.37 ± 0.45 ng / ml, respectively). The results demonstrated the effective role of the aqueous extract of fennel fruits in stimulating estrogen and prolactin in female rats through their content of active compounds, which can be of great importance in stimulating the process of milk secretion in animals.

THE EFFECTS OF TWO ANTIPSYCHOTIC DRUGS AND PROLACTIN ON TOXOPLASMA GONDII TACHYZOITES IN VIVO

Chronic toxoplasmosis is associated with psychotic disorders. Multiple in vitro studiesshowed that many antipsychotic medications have anti-Toxoplasma activity. Meanwhile,there is very limited data regarding the inhibitory effect of them on Toxoplasma in vivo.This study evaluated the activity of Chlorpromazine®, Clozapine®, and prolactin (a pituitarygland hormone) on toxoplasmosis infected rats.Clean laboratory breed rats were chronically infected with non-virulent T. gondii strainand classified into 8 groups: negative, positive control groups, chlorpromazine, clozapine,and metoclopramide drug control groups, and 3 infected treated groups. Rats’ sera werescreened with ELISA test to evaluate level of dopamine, interferon gamma, and prolactin.All drugs were effective against T. gondii in infected rats. Dopamine level and INF-γ levelwere significantly decreased in chlorpromazine infected treated rats. There was significantdecrease of dopamine level and increase of prolactin level in clozapine infected treated rats.In metoclopramide infected treated rats prolactin level significantly increased, but INF-γlevel significantly decreased.

A mutation of the β-domain in POU1F1 causes pituitary deficiency due to dominant PIT-1β expression.

POU1F1 encodes both PIT-1α, which plays pivotal roles in pituitary development and GH, PRL and TSHB expression, and the alternatively spliced isoform PIT-1β, which contains an insertion of 26-amino acids (β-domain) in the transactivation domain of PIT-1α due to the use of an alternative splice acceptor at the end of the first intron. PIT-1β is expressed at much lower levels than PIT-1α and represses endogenous PIT-1α transcriptional activity. Although POU1F1 mutations lead to combined pituitary hormone deficiency (CPHD), no patients with β-domain mutations have been reported. Here, we report that a three-generation family exhibited different degrees of CPHD, including growth hormone deficiency with intrafamilial variability of prolactin/TSH insufficiency and unexpected prolactinoma occurrence. The CPHD was due to a novel POU1F1 heterozygous variant (c.143-69T>G) in intron 1 of PIT-1α (RefSeq number NM_000306) or as c.152T>G (p.Ile51Ser) in exon 2 of PIT-1β (NM_001122757). Gene splicing experiments showed that this mutation yielded the PIT-1β transcript without other transcripts. The lymphocyte PIT-1β mRNA expression was significantly higher in the patients with the heterozygous mutation than a control. A luciferase reporter assay revealed that the PIT-1β-Ile51Ser mutant repressed PIT-1α and abolished transactivation capacity for the rat prolactin promoter in GH3 pituitary cells. We describe, for the first time, that the PIT-1β mutation can cause CPHD through a novel genetic mechanism, such as PIT-1β overexpression, and that POU1F1 mutation might be associated with a prolactinoma. Analysis of new patients and long-term follow-up are needed to clarify the characteristics of PIT-1β mutations.

Study of Serum FSH, LH and Prolactin in Female Albino Rats by Experimentally Creating Hypothyroidism

Objective: The current research was draft to contrast the variation in levels of Prolactin (PRL), Luteinizing Hormone (LH) and Follicle stimulating hormone (FSH) in female rodents by experimentally producing hypothyroidism.Methods: The Animal House of Dow University of Health science was used for the purpose of doing this research which was almost completed in a period of 10 months. The total number of 30 rodents of Wistar Albino species were taken to use in this research. Only adult healthy female rodents weighing between 180-200 gm were included in the study and animals which were found to be slow and lethargic were excluded from the study. These rats were separated into two parts by dividing them into two groups of fifteen animals each. The primary group received the regular normal diet and routine tap water for six weeks and was labeled as the control group whereas the other group was forced to accept Carbimazole (Antithyroid drug) through feeding tube by mixing 0.02% / ml of regular drinking water for a period of six weeks. After six weeks all the rats were slaughtered. The cardiac puncture of animal was done in order to collect blood. Analysis of Follicle Stimulating Hormone, Luteinizing Hormone and Prolactin was carried out by using the ELISA kits on serum of animal which was centrifuged and separated.Results: The result observed for control group showed a mean value ± standard deviation(SD) of 5.13 ± 1.39 mIU/ml for Follicle Stimulating Hormone. In the same group the mean value ± SD observed for Luteinizing Hormone was 8.38 ± 16.02 mIU/ml and for PRL was 0.40 ± 0.05 ng/ml respectively. The second group that is the hypothyroid group revealed a mean value ± (SD) of 5.89 ± 1.63 mIU/ml for Follicle Stimulating Hormone. For Luteinizing Hormones in hypothyroid group, the mean value ± SD turned out to be 9.30 ± 13.34 mIU/ml whereas the mean value ± SD observed for Prolactin in hypothyroid group was 0.62 ± 0.12 ng/ml. The information was entered on SPSS version 16. This information was analysed by applying an independent sample t-test in between the two groups to compare the levels of Follicle Stimulating Hormone, Luteinizing Hormone and PRL. The p-value was observed which turned out to be insignificant for Follicle Stimulating Hormone and Luteinizing Hormone but quite remarkable for Prolactin.Conclusion: Hypothyroidism created by an antithyroid drug (Carbimazole) leads to a remarkable rise in the levels of PRL regardless of the changes in levels of gonadotropins which may lead to the sterility in females.

Comparative assessment of effect of malt with different bud length on prolactin in hyperprolactinemia rat

Malt is the mature fruit of Hordeum vulgare L. after germination and drying and has been applied for treatment female abnormal galactorrhea. Previous studies have showed total alkaloids in malt have anti-HPRL effect. However, total alkaloids of malt change with the growth cycle, and the specified levels of total alkaloids in different bud length of malt have not been decided. To determine the definitive level of total alkaloids in different buds of malt and the most suitable bud length for clinical application by comparing effects on hyperprolactinemia rat. During the budding of malt, the content of total alkaloids first increased and then decreased, and it peaked at a bud length of 0.75 cm. Treated the HPRL model rats with different buds of malt, the PRL level was decreased, the number of PRLpositive cells and the mRNA expression level in the pituitary were significantly declined, and the number of dopamine D1 and D2 receptors in the hypothalamus was increased. The above changes were most significant in 0.75 cm bud. These results suggest that in terms of the content of effective substance and the effects on HPRL model rats, a malt bud length of 0.75 cm is optimal for clinical application.

Diverse effects of phytoestrogen biochanin A on rat pituitary tumor cells

Biochanin A, a nonsteroidal estrogen present in plants, has been suggested in epidemiological studies to be associated with a reduced risk of hormone-related cancers. In this study, we examined the effects of biochanin A on the cell growth and gene expression of an estrogen-responsive pituitary cell line GH3. Results showed that biochanin A inhibited growth of GH3 cells in a dose-dependent manner and at physiologically relevant concentrations. At concentrations of 1 and 5 μg/mL, inhibition of cell growth was observed. The gene expressions of estrogen receptor (ER) mRNA and an estrogen responsive gene, the progesterone receptor (PR), were down-regulated by the biochanin A treatment. In addition, co-administration of antiestrogen ICI182,780 blocked this biochanin A induced down-regulation of the ER and PR mRNA level. However, the expression level of rat prolactin (rPRL) gene, one of the typical estrogen responsive genes, was not regulated by biochanin A. These results indicated that biochanin A at physiologically achieveable concentrations was able to inhibit cell growth of estrogen-responsive rat pituitary cells. In addition, dietary-derived biochanin A compounds exhibit diverse estrogenic and antiestrogenic effects on estrogen-related gene expression, suggesting gene-specific regulation.

Identification of a novel somatic mutation of POU6F2 by whole-genome sequencing in prolactinoma.

BackgroundPituitary adenomas (PAs) are one of the most common intracranial tumors; approximately half of PAs are prolactin (PRL)‐secreting PAs (prolactinomas). The genetic alterations prevalent in prolactinomas are unknown.MethodsHere, we present a patient with an extremely aggressive and giant prolactinoma accompanied by serious destruction of the surrounding bone mass. This patient exhibited resistance to dopaminergic drugs. Through whole‐genome sequencing, we identified two novel somatic mutations in the POU6F2 gene (NM_001166018.2: c. 839 C>T; NM_001166018.2: c. 875A>G).ResultsThis report is the first to identify these somatic mutations in the POU6F2 gene in a prolactinoma. We found that these two mutations obviously decreased the expression level of POU6F2. Inhibition of POU6F2 activity increased the cell proliferation and PRL secretion in rat pituitary cells, but proliferation and PRL secretion were decreased in cells with POU6F2 overexpression.Conclusions POU6F2 might play a crucial role in the development of prolactinomas and may be a promising target for developing new therapies against prolactinomas.

Rapid prolactin induction in adult male rats after treatment with diethylstilbestrol.

Diethylstilbestrol (DES) is a synthetic oestrogen known to disrupt the endocrine system and to cause reproductive toxicity mediated via the hypothalamic-pituitary-adrenal axis; however, its molecular mechanism of action is poorly understood. In the present study, we found that, after only 1week of exposure to DES, blood testosterone dramatically decreased and that this decrease was associated with a strong induction of prolactin (PRL). Even with the increase in PRL, the luteinising hormone and follicle-stimulating hormone mRNAs slightly decreased. Our results show that, after 48hours of a single dose of DES, there was a six-fold increase in PRL expression. After exploring the upstream mechanisms, we determined that dopamine, which inhibits PRL secretion in male rats, did not decrease in the pituitary gland of DES-treated rats, whereas vasoactive intestinal peptide (VIP), which mediates the acute release of PRL, was elevated. Serotonin (5-HT) increased in the brain of male rats 24hours after a single DES treatment; however, PRL, VIP or 5-HT was not induced by DES in female rats. Our results indicate that DES induces the expression of pituitary PRL in male rats by stimulating VIP in the hypothalamus and 5-HT in the central nervous system.

A Spontaneous Aggressive ERα+ Mammary Tumor Model Is Driven by Kras Activation

The NRL-PRL murine model, defined by mammary-selective transgenic rat prolactin ligand rPrl expression, establishes spontaneous ER+ mammary tumors in nulliparous females, mimicking the association between elevated prolactin (PRL) and risk for development of ER+ breast cancer in postmenopausal women. Whole-genome and exome sequencing in a discovery cohort (n= 5) of end-stage tumors revealed canonical activating mutations and copy number amplifications of Kras. The frequent mutations in this pathway were validated in an extension cohort, identifying activating Ras alterations in 79% of tumors (23 of 29). Transcriptome analyses over the course of oncogenesis revealed marked alterations associated with Ras activity in established tumors compared with preneoplastic tissues; in cell-intrinsic processes associated with mitosis, cell adhesion, and invasion; as well as in the surrounding tumor environment. These genomic analyses suggest that PRL induces a selective bottleneck for spontaneous Ras-driven tumors that may model a subset of aggressive clinical ER+ breast cancers.

AFAP1-AS1 Promotes Proliferation of Pituitary Adenoma Cells through miR-103a-3p to Activate PI3K/AKT Signaling Pathway

We previously found that AFAP1-AS1 regulates the cell growth of pituitary tumor cells; however, the mechanism still remains unclear. Here, we investigated whether AFAP1-AS1 acts as a competing endogenous RNA of miR-103a-3p to regulate pituitary adenoma growth via the PI3K/AKT pathway. The bind between AFAP1-AS1 and rno-miR-103a-3p was measured by luciferase reporter assay, and rno-miR-103a-3p expression was measured by quantitative reverse transcription polymerase chain reaction. Proliferation, cell cycle, and apoptosis were measured by cell counting kit 8 and flow cytometry. Rat growth hormone (GH) and prolactin (PRL) levels in culture supernatant of GH3 and MMQ cells were measured by enzyme-linked immunosorbent assay. AFAP1-AS1 binds to rno-miR-103a-3p in rat pituitary adenoma cells. Additionally, rno-miR-103a-3p overexpression suppressed rat pituitary adenoma cell proliferation, induced cell apoptosis, arrested cell cycle in the G/S phase, reduced GH and PLR secretion, and inhibited the PI3K/AKT signaling pathway. Activated PI3K/AKT signaling pathway revised the effect of rno-miR-103a-3p overexpression on proliferation and GH and PLR secretion. Coexpression of both si-AFAP1-AS1 and rno-miR-103a-3p inhibitor promoted cell proliferation and cell cycle progression, reduced cell apoptosis, enhanced GH and PLR secretion, and activated thePI3K/AKT signaling pathway in rat pituitary adenoma cells. We found that AFAP1-AS1 and miR-103a-3p could be a potential therapeutic target for pituitary adenoma.

Prepuberal stress and obesity: effects onserum corticosterone, prolactin, testosterone andprecancerous prostate lesions in adult rats.

In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) or obesity on the development of precancerous lesions in rats. Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5weeks of age). In adulthood (8weeks old), subgroups of males were fed with hypercaloric liquid diet to induce obesity. This resulted in a total of six subgroups: (1)intact-non obese, (2) intact-obese, (3) saline-non obese, (4) saline-obese, (5) LPS-non obese, and (6) LPS-obese. At 16weeks of age the rats were sacrified for prostate histology (hematoxylin and eosin stain) and hormone analysis (testosterone, corticosterone and prolactin). As compared to intact-non obese rats, males treated with LPS and those with obesity expressed histological alterations in both the dorsolateral and ventral portions of the prostate. Only prolactin was altered in LPS-treated males, whereas corticosterone was altered in LPS-obese rats. These results indicate that puberal exposure to an immune challenge or obesity facilitate the development of prostatic lesions in adult male rats. We discuss the role of hormones in the development of precancerous lesions.

Differential activity of 16K rat prolactin in different organic systems

ABSTRACTThe 16K isoform of rat prolactin (16K rPRL) performs multiple functions in various systems including angiogenesis, tumorigenesis, and reproduction. Recently, 16K rPRL has attained prominence as a possible therapeutic target in pathophysiological conditions. However, the integral function and mechanism of 16K rPRL in various systems has not been elucidated. To this end, a transient gain-of-function animal model was adopted. An expression DNA plasmid containing 16K rPRL or rPRL gene was introduced into the muscle of adult mice by direct injection. The mRNA and protein expression levels of 16K rPRL were detected by initial RT–PCR and subsequent Southern blot and western blot, respectively. When the expression vector was introduced, the results were as follows: First, 16K rPRL combined with rPRL reduced angiogenesis in the testis whereas rPRL alone induced angiogenesis. Second, 16K rPRL combined with rPRL reduced WBC proliferation, whereas rPRL alone increased WBC proliferation. Third, 16K rPRL combined with rPRL reduced diestrus, whereas rPRL alone extended diestrus. Fourth, 16K rPRL combined with rPRL unexpectedly increased testosterone (T) levels, whereas rPRL alone did not increase T levels. Taken together, our data suggest that the 16K rPRL isoform performs integral functions in angiogenesis in the testis, WBC proliferation, and reproduction, although the action of 16K rPRL is not always antagonistic.