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1.
Anim Sci J ; 90(11): 1444-1452, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486226

RESUMO

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.


Assuntos
Cervos/metabolismo , Cervos/fisiologia , Implantação do Embrião/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Endométrio/metabolismo , Estradiol/genética , Estradiol/metabolismo , Feminino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Gravidez , Progesterona/genética , Progesterona/metabolismo , RNA Mensageiro/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo
2.
J Agric Food Chem ; 67(34): 9532-9542, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31369265

RESUMO

Murine mammary gland is an ideal model for studying the development and milk synthesis in dairy animals. MicroRNAs play an important role in milk synthesis and mammary gland development; however, the molecular mechanism of miR-142-3p continues to be poorly understood. Here, we knocked down miR-142-3p expression in vitro and vivo, increased the prolactin receptor expression and activated many downstream cellular proteins, such as mammalian target of rapamycin, sterol regulatory element-binding transcription factor 1, cyclin D1, and signal transducer and activator of transcription 5. Additionally, miR-142-3p knockdown in mouse mammary gland epithelial cells increased proliferation but not viability, induced cell cycle progression, decreased apoptosis, and increased the expression of triglycerides and ß-casein. Moreover, miR-142-3p knockdown in murine mammary gland tissue in vivo affected the structure and function of the mammary gland, which showed an increased number of lobules and ducts and was more capable of producing milk. However, overexpression of miR-142-3p had the opposite effects. In summary, these data reveal that miR-142-3p regulates milk synthesis and the structure of murine mammary glands via PRLR-mediated multiple signaling pathways.


Assuntos
Glândulas Mamárias Animais/metabolismo , MicroRNAs/metabolismo , Leite/metabolismo , Receptores da Prolactina/metabolismo , Animais , Caseínas/metabolismo , Células Epiteliais/metabolismo , Feminino , Glândulas Mamárias Animais/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Receptores da Prolactina/genética , Transdução de Sinais , Triglicerídeos/metabolismo
3.
Biochemistry (Mosc) ; 84(4): 329-345, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31228925

RESUMO

The review describes functional and structural features of different isoforms of prolactin receptor, mechanisms of signaling pathway activation, and molecular messengers involved in the transmission and termination of signal from the prolactin receptor isoforms. Changes in the ratio between prolactin receptor isoforms, key mediators of prolactin signal transduction and termination in various organs and tissues, are analyzed. Special attention is given to the role of molecular mediators and the ratio between the isoforms in normal physiological functions and pathologies. Approaches for therapeutic correction of prolactin signaling impairments are discussed.


Assuntos
Prolactina/metabolismo , Receptores da Prolactina/metabolismo , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Inibidoras de STAT Ativados/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores da Prolactina/genética , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/metabolismo
4.
Int J Mol Sci ; 20(7)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987013

RESUMO

The epithelial-mesenchymal transition (EMT) process is known to play an essential role in tumor progression, metastasis and resistance to therapy. This report evaluated the prognostic value of co-expression of the receptor for prolactin (PRLR), a suppressor of EMT, and the receptors for transforming growth factor ß (TGFßRI and TGFßRII), an inducer of EMT, in association with different clinicopathological parameters using TMA of 102 breast cancer patients and publicly available data on breast cancer patients. Interestingly, the results revealed that malignant tissues had significantly lower levels of concomitant protein expression of these receptors in comparison to normal/benign breast tissue. In addition, a higher level of concomitant expression was also observed in less aggressive breast cancer phenotypes, including low grade tumors, luminal breast cancer subtype, and less advanced stages of the disease (lymph node negative and early stages). Moreover, the results also showed that the expression of a gene signature composed of PRLR/TGFßRI/TGFßRII correlates more with differentiated grade I tumors, and identified a subset of patients showing better survival outcomes evident in luminal B and HER-2 enriched molecular subtypes. Together, these results indicate that loss of the co-expression of PRLR, TGFßRI and TGFßRII is indicative of aggressiveness and poor patient survival outcomes in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptores da Prolactina/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Neoplasias da Mama/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Gradação de Tumores , Invasividade Neoplásica , Fenótipo , Receptores da Prolactina/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Análise de Sobrevida , Resultado do Tratamento
5.
Endocrinology ; 160(5): 1150-1163, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004482

RESUMO

Pancreatic ß-cells undergo profound hyperplasia during pregnancy to maintain maternal euglycemia. Failure to reprogram ß-cells into a more replicative state has been found to underlie susceptibility to gestational diabetes mellitus (GDM). We recently identified a requirement for prolactin receptor (PRLR) signaling in the metabolic adaptations to pregnancy, where ß-cell-specific PRLR knockout (ßPRLRKO) mice exhibit a metabolic phenotype consistent with GDM. However, the underlying transcriptional program that is responsible for the PRLR-dependent metabolic adaptations during gestation remains incompletely understood. To identify PRLR signaling gene regulatory networks and target genes within ß-cells during pregnancy, we performed a transcriptomic analysis of pancreatic islets isolated from either ßPRLRKO mice or littermate controls in late gestation. Gene set enrichment analysis identified forkhead box protein M1 and polycomb repressor complex 2 subunits, Suz12 and enhancer of zeste homolog 2 (Ezh2), as novel candidate regulators of PRLR-dependent ß-cell adaptation. Gene ontology term pathway enrichment revealed both established and novel PRLR signaling target genes that together promote a state of increased cellular metabolism and/or proliferation. In contrast to the requirement for ß-cell PRLR signaling in maintaining euglycemia during pregnancy, PRLR target genes were not induced following high-fat diet feeding. Collectively, the current study expands our understanding of which transcriptional regulators and networks mediate gene expression required for islet adaptation during pregnancy. The current work also supports the presence of pregnancy-specific adaptive mechanisms distinct from those activated by nutritional stress.


Assuntos
Regulação da Expressão Gênica , Células Secretoras de Insulina/metabolismo , Receptores da Prolactina/genética , Transdução de Sinais/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Células Secretoras de Insulina/citologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Gravidez , Receptores da Prolactina/metabolismo
6.
Nat Rev Endocrinol ; 15(6): 356-365, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30899100

RESUMO

The principal role of prolactin in mammals is the regulation of lactation. Prolactin is a hormone that is mainly synthesized and secreted by lactotroph cells in the anterior pituitary gland. Prolactin signalling occurs via a unique transmembrane prolactin receptor (PRL-R). The structure of the PRL-R has now been elucidated and is similar to that of many biologically fundamental receptors of the class 1 haematopoietic cytokine receptor family such as the growth hormone receptor. The PRL-R is expressed in a wide array of tissues, and a growing number of biological processes continue to be attributed to prolactin. In this Review, we focus on the newly discovered roles of prolactin in human health and disease, particularly its involvement in metabolic homeostasis including body weight control, adipose tissue, skin and hair follicles, pancreas, bone, the adrenal response to stress, the control of lactotroph cell homeostasis and maternal behaviour. New data concerning the pathological states of hypoprolactinaemia and hyperprolactinaemia will also be presented and discussed.


Assuntos
Pleiotropia Genética/fisiologia , Nível de Saúde , Hiperprolactinemia/metabolismo , Osteoporose/metabolismo , Prolactina/metabolismo , Animais , Feminino , Homeostase/fisiologia , Humanos , Hiperprolactinemia/genética , Osteoporose/genética , Prolactina/deficiência , Prolactina/genética , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo
7.
Endocrinology ; 160(5): 1323-1332, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901026

RESUMO

Hyperprolactinemia causes infertility, but the specific mechanism is unknown. It is clear that elevated prolactin levels suppress pulsatile release of GnRH from the hypothalamus, with a consequent reduction in pulsatile LH secretion from the pituitary. Only a few GnRH neurons express prolactin receptors (Prlrs), however, and thus prolactin must act indirectly in the underlying neural circuitry. Here, we have tested the hypothesis that prolactin-induced inhibition of LH secretion is mediated by kisspeptin neurons, which provide major excitatory inputs to GnRH neurons. To evaluate pulsatile LH secretion, we collected serial blood samples from diestrous mice and measured LH levels by ultrasensitive ELISA. Acute prolactin administration decreased LH pulses in wild-type mice. Kisspeptin neurons in the arcuate nucleus and in the rostral periventricular area of the third ventricle (RP3V) acutely responded to prolactin, but prolactin-induced signaling in kisspeptin neurons was up to fourfold higher in the arcuate nucleus when compared with the RP3V. Consistent with this, conditional knockout of Prlr specifically in arcuate nucleus kisspeptin neurons prevented prolactin-induced suppression of LH secretion. Our data establish that during hyperprolactinemia, suppression of pulsatile LH secretion is mediated by Prlr on arcuate kisspeptin neurons.


Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Kisspeptinas/metabolismo , Hormônio Luteinizante/metabolismo , Neurônios/efeitos dos fármacos , Prolactina/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/citologia , Núcleo Arqueado do Hipotálamo/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hiperprolactinemia/genética , Hiperprolactinemia/metabolismo , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/fisiologia , Prolactina/administração & dosagem , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo
8.
Eur J Histochem ; 63(1)2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30652434

RESUMO

Prolactin (PRL) production in mammals has been demonstrated in extrapituitary gland, which can activate autocrine/paracrine signaling pathways to regulate physiological activity. In the current study, we characterized the gene expression profiles of PRL, prolactin receptor (PRLR) and signal transducers and activators of transcription 5 (STAT5) in the scented glandular tissues of the muskrats, to further elucidate the relationship between PRL and the scented glandular functions of the muskrats. The weight and volume of the scented glands in the breeding season were significantly higher than those of the non-breeding season. Immunohistochemical data showed that PRL, PRLR and STAT5/phospho-STAT5 (pSTAT5) were found in the glandular and epithelial cells of the scented glands in both seasons. Furthermore, we found that PRL, PRLR and STAT5 had higher immunoreactivities in the scented glands during the breeding season when compared to those of the non-breeding season. In parallel, the gene expressions of PRL, PRLR and STAT5 were significantly higher in the scented glands during the breeding season than those of the non-breeding season. The concentrations of PRL in scented glandular tissues and sera were measured by enzyme-linked immunosorbent assay (ELISA), and their levels were both notably higher in the breeding season than those of the non-breeding season. These findings suggested that the scented glands of the muskrats were capable of extrapituitary synthesis of PRL, which might attribute PRL a specific function to an endocrine or autocrine/paracrine mediator.


Assuntos
Regulação da Expressão Gênica , Prolactina/genética , RNA Mensageiro/metabolismo , Receptores da Prolactina/genética , Fator de Transcrição STAT5/genética , Glândulas Odoríferas/metabolismo , Animais , Arvicolinae , Imuno-Histoquímica , Masculino , Receptores da Prolactina/metabolismo , Reprodução/fisiologia , Fator de Transcrição STAT5/metabolismo , Estações do Ano
9.
Reprod Fertil Dev ; 31(4): 735-742, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30509341

RESUMO

Luteinising hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) are pituitary-derived hormones and mediate their functions through LH receptor (LHR), FSH receptor (FSHR) and PRL receptor (PRLR) respectively. This study aimed to investigate the seasonal expression patterns of LHR, FSHR and PRLR in the epididymis of the male wild ground squirrel during the breeding and non-breeding seasons. Histologically, principal cells, basal cells, cilia and mature spermatozoa were found in the lumen of caput, corpus and cauda epididymidis in the breeding season, whereas in the non-breeding season, cilia and basal cells were rarely found and the epididymidal duct was devoid of spermatozoa. Immunohistochemical results showed that LHR, FSHR and PRLR were mainly present in the filamentous cytoplasm layer of epithelial cells of the caput, corpus and cauda epididymidis and FSHR and PRLR displayed stronger staining in the breeding season than in the non-breeding season. Furthermore, the mRNA and protein levels of FSHR and PRLR in all regions of epididymis as well as the levels of LHR in the caput and cauda epididymidis were higher during the breeding season. The protein levels of FSHR, LHR and PRLR were positively correlated with epididymal weight. Together, these results suggest that LHR, FSHR and PRLR may regulate epididymal functional changes in the male wild ground squirrel during its seasonal breeding cycle.


Assuntos
Epididimo/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Receptores da Prolactina/metabolismo , Estações do Ano , Animais , Masculino , Receptores do FSH/genética , Receptores do LH/genética , Receptores da Prolactina/genética , Reprodução/fisiologia , Sciuridae , Testículo/metabolismo
10.
J Anim Sci ; 97(1): 220-230, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321363

RESUMO

The impact of body condition in late gestating gilts on gene expression of selected adipokines and their receptors in backfat and mammary fat tissues was studied. The presence of associations between mammary gland composition variables and the mRNA abundance of selected genes and serum concentrations of adiponectin and leptin was also investigated. A total of 45 gilts were selected at mating based on their backfat depth and were allocated to three groups: (1) low backfat (LBF; 12-15 mm; n = 14), (2) medium backfat (MBF; 17-19 mm; n = 15), and (3) high backfat (HBF; 22-26 mm; n = 16). Gilts were fed different amounts of a conventional diet to maintain differences in backfat depth throughout the gestation period. Blood samples were collected at day 109 of gestation to measure adiponectin and leptin serum concentrations. Gilts were slaughtered on day 110 of gestation, and mammary glands were collected to determine mammary composition. Mammary fat and backfat tissues were also sampled to measure the mRNA abundance of selected genes. In mammary fat tissue, there was an effect of body condition on the prolactin (PRL; P = 0.01), adiponutrin (PNPLA3; P < 0.10), and prolactin receptor long form (PRLR-LF; P < 0.10) genes. There was a greater PRL mRNA abundance in mammary fat tissue from HBF than LBF or MBF gilts (P < 0.05). The PNPLA3 mRNA abundance was lower in HBF than in MBF gilts (P < 0.05), and that of PRLR-LF was lower in LBF than in HBF gilts (P < 0.05). In backfat, body condition affected the mRNA abundance of leptin (P < 0.05) and PNPLA3 (P < 0.01), with the greatest expression levels being observed in HBF gilts for both genes. Association analyses suggest a detrimental effect of high circulating leptin concentrations on gilts mammary development, as reflected by the negative correlations between serum leptin and protein percent (r = -0.66, P < 0.01), and concentrations of DNA (r = -0.62, P < 0.01) and RNA (r = -0.60, P < 0.01) in mammary parenchyma. Current results show that body condition of gilts at the end of gestation can affect the expression of adipokines in mammary fat and backfat tissues, with a different regulation of transcript abundance being observed in these two fat depots. Results also suggest that circulating leptin is strongly associated with mammary gland composition of late pregnant gilts, whereas locally synthesized leptin from mammary fat tissue is not.


Assuntos
Adipocinas/genética , Proteínas de Membrana/sangue , Receptores da Prolactina/genética , Suínos/fisiologia , Adipocinas/sangue , Adiponectina/sangue , Adiponectina/genética , Tecido Adiposo/fisiologia , Animais , Composição Corporal , Dieta/veterinária , Feminino , Leptina/sangue , Leptina/genética , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana/genética , Gravidez , Prolactina/sangue , Prolactina/genética , RNA Mensageiro/genética , Receptores da Prolactina/sangue , Suínos/sangue , Suínos/genética
11.
N Engl J Med ; 379(23): 2230-2236, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30575453

RESUMO

A loss-of-function variant in the gene encoding the prolactin receptor ( PRLR) was reported previously in a woman with persistent postpartum galactorrhea; however, this paradoxical phenotype is not completely understood. Here we describe a 35-year-old woman who presented with idiopathic hyperprolactinemia that was associated with a complete lack of lactation after each of her two deliveries. She is a compound heterozygote for loss-of-function variants of PRLR. Her unaffected parents are heterozygotes. These findings are consistent with previous work showing that mice deficient in functional Prlr do not lactate.


Assuntos
Hiperprolactinemia/genética , Transtornos da Lactação/genética , Mutação com Perda de Função , Receptores da Prolactina/genética , Adulto , Feminino , Variação Genética , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Linhagem , Prolactina/sangue , Hormônio Liberador de Tireotropina
12.
Gen Comp Endocrinol ; 269: 102-111, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30172709

RESUMO

Pituitary prolactin (PRL) shows an episodic pattern of evolution in mammals, with a slow underlying rate (near stasis) and periods of rapid change in some groups. PRL evolution in bats, the second most speciose mammalian order, has not previously been studied, and is examined here. Slow basal evolution of PRL is seen in some bats, particularly megabats, but in most microbat groups evolution of PRL is more rapid. Accelerated evolution of PRL is particularly notable in the family Vespertilionidae, where analysis of nonsynonymous and synonymous substitutions indicates that it reflects adaptive evolution/positive selection. Remarkably, vespertilionid bats also show a large sequence insertion, of variable length, into exon 4 of PRL, giving a protein sequence 18-60 amino acids longer than normal, with the longest insertions in bats of the genus Myotis. An equivalent insertion has not been reported in PRL of any other vertebrate group. In the 3-dimensional structure of the complex between PRL and the extracellular domain (ecd) of its receptor (PRL:PRLR2) the inserted sequence is seen to be introduced in the short loop between helices 2 and 3 of PRL; it is far removed from the receptor-binding sites, and may not interfere with binding. The ecd of the receptor also shows variable rates of evolution, with a higher rate in the Vespertilionidae, but this is much less marked than for the hormone. The distribution of substitutions introduced into PRL during vespertilionid evolution appears to be non-random, and this and the evidence for positive selection suggests that the rapid evolution and insert sequence introduction were associated with a significant change in the biological properties of the hormone.


Assuntos
Quirópteros/genética , Evolução Molecular , Mutagênese Insercional/genética , Prolactina/genética , Sequência de Aminoácidos , Animais , Modelos Moleculares , Filogenia , Prolactina/química , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Transcrição Genética
13.
Endocrine ; 62(3): 681-691, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30143940

RESUMO

INTRODUCTION AND AIM: Hyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR. RESULTS: Expression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group. CONCLUSIONS: Downregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.


Assuntos
Osso e Ossos/metabolismo , Duodeno/metabolismo , Hiperprolactinemia/metabolismo , Rim/metabolismo , Receptores da Prolactina/metabolismo , Animais , Cálcio/sangue , Feminino , Hiperprolactinemia/induzido quimicamente , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Fósforo/sangue , Gravidez , Ratos , Ratos Wistar , Receptores da Prolactina/genética , Sulpirida
14.
J Chem Neuroanat ; 94: 1-7, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30118754

RESUMO

The eusocial Damaraland mole-rat (Fukomys damarensis) represents an extreme example of reproductive skew, in that reproduction is completely blocked in female subordinate group members. It is thought that in these animals normal GnRH secretion from the hypothalamus is disrupted. Prolactin, a peptide hormone secreted from the anterior pituitary gland, has been implicated in a wide variety of functions. Well documented in rodents is its role in mediating lactational infertility. Elevated circulating prolactin levels, such as during lactation, are associated with reduced GnRH release into the portal blood and with a reduction in the frequency and amplitude of LH pulses. The present study aimed at investigating whether such a mechanism could act in reproductively suppressed female Damaraland mole-rats. By means of in situ hybridisation we studied the distribution and gene expression of the prolactin receptor (Prlr) in wild-caught female Damaraland mole-rats with different reproductive status. Substantial Prlr expression was found in several brain regions, with highest levels in the choroid plexus and moderate expression in the preoptic and tuberal hypothalamus. While in reproductive and non-reproductive females plasma prolactin levels were very low and not significantly different, quantification of the Prlr hybridisation signal revealed significant differences in relation to reproductive status. Reproductively suppressed females had increased expression of Prlr in the choroid plexus and in the arcuate nucleus (ARC) when compared to reproductive females. This suggests higher local prolactin levels in the brain of suppressed females. Together with previous findings, it could indicate that prolactin inhibits ARC kisspeptin neurons, which then would lead to reduced activation of GnRH neurons in such females.


Assuntos
Plexo Corióideo/metabolismo , Hipotálamo/metabolismo , Prolactina/sangue , Receptores da Prolactina/metabolismo , Reprodução/fisiologia , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Ratos-Toupeira , Neurônios/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Prolactina/genética
15.
J Neuroendocrinol ; 30(9): e12634, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30040149

RESUMO

Prolactin influences a wide range of physiological functions via actions within the central nervous system, as well as in peripheral tissues. A significant limitation in studies investigating these functions is the difficulty in identifying prolactin receptor (Prlr) expression, particularly in the brain. We have developed a novel mouse line using homologous recombination within mouse embryonic stem cells to produce a mouse in which an internal ribosome entry site (IRES) followed by Cre recombinase cDNA is inserted immediately after exon 10 in the Prlr gene, thereby targeting the long isoform of the Prlr. By crossing this Prlr-IRES-Cre mouse with a ROSA26-CAGS-tauGFP (τGFP) reporter mouse line, and using immunohistochemistry to detect τGFP, we were able to generate a detailed map of the distribution of individual Prlr-expressing neurones and fibres throughout the brain of adult mice without the need for amplification of the GFP signal. Because the τGFP is targeted to neurotubules, the labelling detected not only cell bodies, but also processes of prolactin-sensitive neurones. In both males and females, Cre-dependent τGFP expression was localised, with varying degrees of abundance, in a number of brain regions, including the lateral septal nucleus, bed nucleus of the stria terminalis, preoptic and hypothalamic nuclei, medial habenula, posterodorsal medial amygdala, and brainstem regions such as the periaqueductal grey and parabrachial nucleus. The labelling was highly specific, occurring only in cells where we could also detect PrlrmRNA by in situ hybridisation. Apart from two brain areas, the anteroventral periventricular nucleus and the medial preoptic nucleus, the number and distribution of τGFP-immunopositive cells was similar in males and females, suggesting that prolactin may have many equivalent functions in both sexes. These mice provide a valuable tool for investigating the neural circuits underlying the actions of prolactin.


Assuntos
Encéfalo/metabolismo , Genes Reporter , Neurônios/metabolismo , Receptores da Prolactina/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Prolactina/metabolismo , Receptores da Prolactina/genética
16.
Nutrients ; 10(6)2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29899203

RESUMO

The aim of this study was to investigate the effect of dietary daidzein supplementation on reproductive performance in rats. A total of twenty-four female Sprague⁻Dawley (SD) rats were randomly allocated to two groups and fed either with a basal diet (CON) or basal diet containing 50 mg/kg daidzein (DAI) from gestation until delivery stage. The results show that daidzein supplementation significantly increased the total litter weight and the total viable newborn weight (p < 0.05). Interestingly, daidzein supplementation acutely elevated the concentrations of serum estrogen, progesterone and insulin-like growth factor-1 (p < 0.01) after the maternal rats’ delivery. The concentrations of serum immunoglobulin A (IgA) and immunoglobulin G (IgG) were also significantly higher in the DAI maternal rats than in the CON maternal rats (p < 0.05). Moreover, daidzein significantly increased the total antioxidant capacity (T-AOC) in maternal rats’ sera and in newborns (p < 0.05) and elevated the concentration of superoxide dismutase (SOD) in both the maternal rats’ sera and their ovaries (p < 0.05). Importantly, daidzein supplementation significantly elevated the expression levels of estrogen receptor β (ERβ) and NR5A2 genes in maternal rats’ ovaries (p < 0.05) and downregulated the expression level of prolactin receptor (PRLR) in newborns (p < 0.05). These results suggest that dietary daidzein supplementation improves reproductive performance and fetal development in rats, which is associated with changes in serum hormones, tissue antioxidant capacity, and expression levels of reproductive-related genes, both in maternal rats and their offspring.


Assuntos
Suplementos Nutricionais , Estrogênios/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Isoflavonas/administração & dosagem , Progesterona/sangue , Reprodução/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Peso ao Nascer/efeitos dos fármacos , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Regulação da Expressão Gênica , Idade Gestacional , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Gravidez , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Reprodução/genética , Útero/efeitos dos fármacos , Útero/metabolismo
17.
J Neuroendocrinol ; 30(9): e12613, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29862587

RESUMO

Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood-brain barrier. Accordingly, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL-R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real-time polymerase chain reaction, we found that PRL-R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch-clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 µmol L-1 PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, -6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L-1 to 1 µmol L-1 , the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K+ current in 67% of SFO neurones in voltage-clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL-R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Prolactina/farmacologia , Receptores da Prolactina/metabolismo , Órgão Subfornical/efeitos dos fármacos , Animais , Ciclo Estral/genética , Ciclo Estral/metabolismo , Feminino , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores da Prolactina/genética , Órgão Subfornical/metabolismo , Órgão Subfornical/fisiologia
18.
Trop Anim Health Prod ; 50(8): 1913-1920, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29926362

RESUMO

Prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) are in hormone-response pathways involved in energy metabolism during thermoregulation processes in cattle. Objective herein was to study the association between single nucleotide polymorphisms (SNP) within genes of the PRL and GH/IGF-1 pathways with fertility traits such as services per conception (SPC) and days open (DO) in Holstein cattle lactating under a hot-humid climate. Ambient temperature and relative humidity were used to calculate the temperature-humidity index (THI) which revealed that the cows were exposed to heat stress conditions from June to November of 2012 in southern Sonora, Mexico. Individual blood samples from all cows were collected, spotted on FTA cards, and used to genotype a 179 tag SNP panel within 44 genes from the PRL and GH/IGF-1 pathways. The associative analyses among SNP genotypes and fertility traits were performed using mixed-effect models. Allele substitution effects were calculated using a regression model that included the genotype term as covariate. Single-SNP association analyses indicated that eight SNP within the genes IGF-1, IGF-1R, IGFBP5, PAPPA1, PMCH, PRLR, SOCS5, and SSTR2 were associated with SPC (P < 0.05), whereas four SNP in the genes GHR, PAPPA2, PRLR, and SOCS4 were associated with DO (P < 0.05). In conclusion, SNP within genes of the PRL and GH/IGF-1 pathways resulted as predictors of reproductive phenotypes in heat-stressed Holstein cows, and these SNP are proposed as candidates for a marker-assisted selection program intended to improve fertility of dairy cattle raised in warm climates.


Assuntos
Bovinos/genética , Fertilidade/genética , Receptor IGF Tipo 1/genética , Receptores da Prolactina/genética , Receptores da Somatotropina/genética , Animais , Clima , Feminino , Genótipo , Hormônio do Crescimento , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico , Fator de Crescimento Insulin-Like I , Lactação , México , Fenótipo , Polimorfismo de Nucleotídeo Único , Prolactina , Reprodução , Clima Tropical
19.
Poult Sci ; 97(9): 3092-3096, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788420

RESUMO

Previous study in our lab showed that indigenous Xianju chickens from free-range system (FRS) under summer conditions had lower egg production than those from conventional cage rearing system (CRS). The objective of this study was to preliminarily determine the FRS-dependent mechanism of depressing laying performance according to determining the effect of rearing systems on reproductive hormones secretion and their receptors mRNA expression in Xianju chickens reared under summer conditions. A total of 360 indigenous Xianju chickens were randomly allocated to CRS and FRS groups, each of which included 5 replicates of 36 hens. The experiment lasted between 21 and 29 wk of age. We found that the ovarian weight, numbers of small yellow follicles, and large white follicles in the FRS group were lower than those in the CRS group (P < 0.05). Changing from CRS to FRS increased serum concentrations of prolactin and decreased serum-luteinizing hormone and progesterone levels (P < 0.05). Gene expressions in the preovulatory follicles from FRS hens were upregulated for prolactin receptor and downregulated for luteinizing hormone receptor and progesterone receptor, compared to those from CRS hens (P < 0.05). It can be concluded that changing from CRS to FRS in the current experimental conditions depressed egg production traits in Xianju chickens by inducing a synergistic activity of reproductive hormones and the gene expressions of their receptors.


Assuntos
Criação de Animais Domésticos/métodos , Galinhas/fisiologia , Regulação da Expressão Gênica , Abrigo para Animais , Hormônio Luteinizante/metabolismo , Progesterona/metabolismo , Prolactina/metabolismo , Animais , Galinhas/genética , Feminino , Distribuição Aleatória , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Estações do Ano
20.
FASEB J ; 32(9): 4791-4797, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29596024

RESUMO

Prolactin (PRL), whose principal role is regulation of lactation, is mainly synthesized and secreted by lactotroph anterior pituitary cells. Its signaling is exerted via a transmembrane PRL receptor (PRLR) expressed in a wide variety of tissues, including the anterior pituitary. Dopamine, which is secreted by tuberoinfundibular hypothalamic neurons, is the major inhibitory regulator of prolactin secretion. Although PRL is well established to stimulate hypothalamic dopamine secretion, thereby exerting a negative feedback regulation on its own release, autocrine or paracrine actions of PRL on lactotroph cells have also been suggested. Within the pituitary, PRL may inhibit both lactotroph proliferation and secretion, but in vivo evaluation of these putative functions is limited. To determine whether the autocrine actions of prolactin have a significant role in the physiologic function of lactotrophs in vivo, we examined the consequences of conditional deletion of Prlr in lactotroph cells using a novel mouse line with loxP sites flanking the Prlr gene ( Prlrlox/lox) and Cre-recombinase (Cre) expressed under the control of the pituitary-specific Prl promoter. Prlrlox/lox/Prl-Cre mice have normal PRL levels and did not develop any pituitary lactotroph adenoma, even at 20 mo of age. Nevertheless, Prlrlox/lox/Prl-Cre mice displayed an increased dopaminergic inhibitory tone compared with control Prlrlox/lox mice. These results elegantly confirm an autocrine/paracrine feedback of PRL on lactotroph cells in vivo, which can be fully compensated by an intact hypothalamic feedback system.-Bernard, V., Lamothe, S., Beau, I., Guillou, A., Martin, A., Le Tissier, P., Grattan, D., Young, J., Binart, N. Autocrine actions of prolactin contribute to the regulation of lactotroph function in vivo.


Assuntos
Comunicação Autócrina/fisiologia , Lactotrofos/metabolismo , Prolactina/metabolismo , Receptores da Prolactina/metabolismo , Animais , Hipotálamo/metabolismo , Integrases/metabolismo , Lactação/metabolismo , Camundongos Transgênicos , Hipófise/metabolismo , Adeno-Hipófise/metabolismo , Receptores da Prolactina/genética , Transdução de Sinais/fisiologia
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