Real-Time Visualization of Human Prolactin Alternate Promoter Usage in Vivo Using a Double-Transgenic Rat Model

Semprini, Sabrina; Friedrichsen, Sönke; Harper, Claire V.; McNeilly, J. R.; Adamson, Antony; Spiller, David G.; Kotelevtseva, Nina; Brooker, Gillian; Brownstein, David G.; McNeilly, Alan S.; White, Mike; Davis, John R.; Mullins, John J.

doi:10.1210/me.2008-0399

Cited by 32 publications

(73 citation statements)

References 39 publications

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“…However, a common regulator to all non-pituitary sites, if it exists, is yet to be identified. A very elegant humanized transgenic rat model was recently generated, in which expression of bioluminescent (luciferase) and fluorescent (GFP) reporters were put under the transcriptional control of PRL gene promoters (Semprini et al 2009). This model should be very useful for identifying stimuli regulating extrapituitary expression of PRL in vivo.…”

Section: Prl Not Only An Endocrine Hormonementioning

confidence: 99%

New concepts in prolactin biology

Bernichtein

Touraine²,

Goffin³

2010

Journal of Endocrinology

154

112

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Human prolactin (PRL) is currently viewed as a hormone of pituitary origin, whose production (i.e. serum levels) is controlled by dopamine, whose biological actions relate exclusively to lactation and reproductive functions, for which any genetic disorder is yet to be identified, and whose unique associated pathology is hyperprolactinemia. Both experimental studies and human sample/cohort-based investigations performed during the past decade have considerably widened our perception of PRL biology: i) there are now strong epidemiological arguments supporting the fact that circulating PRL is a risk factor for breast cancer, ii) in addition to the endocrine hormone, locally produced PRL has been documented in several human tissues; there is increasing evidence supporting the tumor growth potency of local PRL, acting via autocrine/paracrine mechanisms, in both rodent models, and human breast and prostate tumors, iii) the first functional germinal polymorphisms of the PRL receptor were recently identified in patients presenting with breast tumors, which involve single amino acid substitution variants exhibiting constitutive activity, iv) human PRL analogs have been engineered, which were shown in experimental models to down-regulate the effects triggered by local PRL (competitive antagonism) or by the constitutively active receptor variants (inverse agonism). The aim of this review is to discuss these novel concepts in PRL biology, including their potential pathophysiological outcomes.

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Section: Prl Not Only An Endocrine Hormonementioning

confidence: 99%

New concepts in prolactin biology

Bernichtein

Touraine²,

Goffin³

2010

Journal of Endocrinology

154

112

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“…PRL is produced mainly in the adenohypophysis, though synthesis in other sites, including brain, has also been described (Méndez, Cariño, & Díaz, 2005; BenJonathan, LaPensee, C.R., & LaPensee, E.W., 2008; Semprini, et al, 2009). Many neurotransmitters are involved in the control of pituitary PRL secretion; in contrast with the rest of the main pituitary hormones, its regulation is mostly inhibitory and is exerted by the neurotransmitter dopamine (DA) released into portal circulation by the dopaminergic neurons of the arcuate and periventricular nuclei of the hypothalamus.…”

Section: Fluctuations In E2 P4 and Prl Levelsmentioning

confidence: 99%

Influence of the estrous cycle on some non reproductive behaviors and on brain mechanisms in the female rat

Jatuff

Torrecilla

Quercetti

et al. 2012

Interd

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El rol de las hormonas sexuales sobre el comportamiento reproductivo ha sido extensamente documentado. La fluctuación periódica de hormonas sexuales en hembras de numerosas especies ha sido relacionada con cambios comportamentales no sexuales tales como humor, ansie dad, agresión y respuesta a estrés. El sustrato bioló-gico-neural de estos cambios se basa en los cambios que estas hormonas inducen en el Sistema Nervioso Central. Este trabajo resume algunos cambios que afectan a receptores y neurotrasmisores de los sistemas GABAérgico, serotoninér-gico, dopaminérgico y péptido liberador de prolactina del SNC de la rata. La rata hembra posee un ciclo sexual de 4 días de duración, denominado ciclo estrual. La presente revisión se informa en tres secciones. (1) Se presenta una breve descripción de la variación de tres hormonas sexuales principales con acción directa sobre el SNC: estrógenos (E2), progesterona (P4) y prolactina (PRL). Se han descripto propiedades ansiolíticas para P4 y anti-estrés para PRL; para E2, la bibliografía es controvertida, describiéndose acciones excitatorias y anti-estrés. (2) Se informan algunos cambios cerebrales y comportamentales que tienen lugar en cada estadio del ciclo estrual. Las fluctuaciones hormonales se consideran bá-sicas para la interpretación de tales cambios. (3) Se mencionan algunos hallazgos acerca de la influencia hormonal cíclica sobre los sistemas de neurotransmisión del SNC y sobre un nuevo pép-tido propuesto como mediador de la respuesta a INTERDISCIPLINARIA, 2012, 29, 1, 63-77 63 INFLUENCE OF THE ESTROUS ABSTRACTSex hormone fluctuations in females are involv ed in some behavioral states such as mood, anxiety, aggression and stress response, due to functional changes in the central nervous system (CNS) activity induced by the cyclic sex hormone fluctuation. This review includes three sections.1.-A description of the three major hormone fluctuations in the estrous cycle: estrogens (E2), progesterone (P4) and prolactine (PRL). E2 achieves the maximum circulation levels during P. E2 is mainly excitatory and has been considered to have an antidepressive action. The highest plasma levels of P4 and its metabolite allopregnenolone (ALLO) occur in P. Ovulation takes place in the night of P, and the resulting corpora lutea produces a secondary increase in P4 (and ALLO) on D. The P4 peak level occurring in D1 and in the evening of P was shown to exert benzodiazepine-like effects, including sedation. It has been proposed that ALLO, rather than P4 is the one acting on GABA systems. Circulating levels of ALLO parallel those of P4 across the estrous cycle and is known to have anxiolytic properties.PRL is produced mainly in the adeno hy pophysis, though synthesis in other sites of the brain also occurs. Its regulation is mostly inhibitory and is exerted by dopamine (DA) released in the hypothalamus. A surge in PRL secretion occurs during P. PRL would be a modulator of the HPA-axis, and is considered as a stress hormone.2.-Some behavioral and neural changes occur at each stage ...

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“…In these circumstances, ectopic expression of human genepromoter constructs in rat pituitary cells is a common approach for assessing the regulation of the human prolactin gene (e.g. Adamson et al 2008, Semprini et al 2009). …”

Section: Choosing a Suitable Cell Model Systemmentioning

confidence: 99%

“…However, transcriptional regulatory mechanisms are highly gene specific and proximalflanking DNA is often insufficient to drive transgene expression (e.g. human GH; Palmiter & Brinster 1986), or at least does not reflect the full promoter behaviour for gene activation (Semprini et al 2009). In such cases, the use of larger constructs has shown the necessity of surrounding genomic sequences, containing enhancers and locus control regions, resulting in a more accurate representation of in vivo gene expression (e.g.…”

Section: Large Constructsmentioning

confidence: 99%

Novel approaches to in vitro transgenesis

Adamson¹,

Jackson²,

Davis³

2010

Journal of Endocrinology

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The study of gene expression is a major focus in biological research and is recognised to be critical for our understanding of physiological and pathophysiological processes. Methods to study gene expression range from in vitro biochemical assays through cultured cells and tissue biopsies to whole organisms. In the early stages of project development, considerations about which model system to use should be addressed and may influence future experimental procedures. The aim of this review is to briefly describe advantages and disadvantages of the existing techniques available to study eukaryote gene expression in vitro, including the mechanism of transgene integration (transient or stable), the different transgenesis systems available, including plasmids, viruses and targeted integration and knockin approaches, and paying particular attention to expression systems such as bacterial artificial chromosomes and episomal vectors that offer a number of advantages and are increasing in popularity. We also discuss novel approaches that combine some of the above techniques, generating increasingly complex but physiologically accurate expression systems.

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Real-Time Visualization of Human Prolactin Alternate Promoter Usage in Vivo Using a Double-Transgenic Rat Model

Cited by 32 publications

References 39 publications

New concepts in prolactin biology

New concepts in prolactin biology

Influence of the estrous cycle on some non reproductive behaviors and on brain mechanisms in the female rat

Novel approaches to in vitro transgenesis

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