Disease relevance of Prl

• The Nb2 cell line is a pre-T rat lymphoma that is dependent on prolactin (PRL) for mitogenesis [1].
• Experiments using an expression vector for adenovirus 12S E1a provided evidence that the coactivators, CREB binding protein and/or p300, probably play a role in cAMP responsiveness of the PRL promoter [2].
• Regulation of Ca2+-dependent cyclic AMP accumulation and Ca2+ metabolism in intact pituitary tumor cells by modulators of prolactin production [3].
• Vasoactive intestinal polypeptide antiserum affects rat prolactin mRNA in 40-day but not 110-day diethylstilbestrol-induced prolactinoma tissue [4].
• Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat [5].
• Antibodies developed by porcine or rat pituitary PRL reduced the bioactivity of rat serum PRL, and gonadal functions in these rats were normal despite hyperprolactinemia [6].

Psychiatry related information on Prl

• Prolactin (PRL) is considered to induce maternal behavior toward foster young in female rats [7].
• In both wehicle- or melatonin-treated rats, food and water deprivation did not affect the OT, PRL and ACTH secretion [8].
• VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL [9].
• Influence of exogenously administered oxytocin on the corticosterone and prolactin response to psychological stress [10].
• Exogenous oxytocin attenuates suckling-induced prolactin release but not maternal or infant behavior in lactating rats [11].

High impact information on Prl

• Prolactin and breast cancer [12].
• Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype [13].
• Prolactin gene expression is negatively regulated by glucocorticoids, and by estrogens when positive estrogen regulatory elements in the prolactin gene are removed [14].
• Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively [13].
• We have shown previously that processing of preprolactin to prolactin in isolated rat pituitaries is inhibited by the threonine analog, beta-hydroxynorvaline (Hnv), presumably because of its substitution for the threonine at the cleavage site [15].

Chemical compound and disease context of Prl

• The responsiveness of anterior pituitary tumor (GH3) cells to promoters of prolactin secretion and/or synthesis and cyclic AMP accumulation was studied as a function of cellular Ca2+ content [3].
• Energy metabolism in rat pituitary tumors during stimulation of prolactin by vasoactive intestinal polypeptide and thyrotropin-releasing hormone: a study with nuclear magnetic resonance spectroscopy [16].
• An analogue of creatine increases TRH-stimulated prolactin secretion and phosphoinositide hydrolysis in rat pituitary tumor cells [17].
• Prolactin (PRL) is essential for progesterone biosynthesis and luteal cell hypertrophy of the rat corpus luteum during pregnancy [18].
• During late pregnancy and lactation, the tuberoinfundibular dopamine (TIDA) neurons that regulate prolactin secretion by negative feedback become less able to produce dopamine in response to prolactin, leading to hyperprolactinemia [19].

Biological context of Prl

• The effects of pituitary and extrapituitary prolactin include cellular proliferation and differentiation [20].
• Prolactin acted as a mitogen for undifferentiated PC12 cells, as measured by significant increases in bromodeoxyuridine incorporation and in cell numbers, with an efficacy equal to epidermal growth factor [20].
• Ca2+ increased all large prolactin RNA sequences in the nucleus, thus suggesting a transcriptional site of action [21].
• Consistent with the role of PKCdelta in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cgamma (PLCgamma) activity [22].
• As previous studies have implicated Ets factor binding sites within the PRL promoter in mediating responses to MAPK, we expected that the Ets sites would also play a role in cAMP responsiveness [2].

Anatomical context of Prl

• Thus, Prl and the beta 2-agonist stimulate progesterone production in granulosa cells by increasing pregnenolone production and 3 beta-HSD activity as well as by decreasing 20 alpha-HSD activity, while hCG stimulates progesterone production by increasing pregnenolone production and 3 beta-HSD activity [23].
• A prolactin-dependent immune cell line (Nb2) expresses a mutant form of prolactin receptor [1].
• Our studies suggest that prolactin may have a role in the growth of PC12 cells, where it stimulates concurrent mitogenic and differentiation-promoting signaling pathways [20].
• These results demonstrate that PRL/rPL-1 promotes relaxin expression in luteal cells and that this event is mediated, at least in part, via PKC delta [24].
• Fibroblast growth factors regulate prolactin transcription via an atypical Rac-dependent signaling pathway [22].

Associations of Prl with chemical compounds

• Concomitant treatment with GnRH inhibited progesterone, but increased 20 alpha-OH-P production stimulated by Prl or terbutaline [23].
• Subsequent treatment for 2 days with Prl, terbutaline (a beta 2-adrenergic agonist) or hCG stimulated the production of progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P), pregnenolone and the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) [23].
• In pituitary lactotrophs the prolactin gene is stimulated by neuropeptides and estrogen and is suppressed by dopamine via D2-type receptors [25].
• Here we show that in prolactin-secreting GH4ZR7 cells and primary pituitary cells, dopamine treatment leads to a rapid, pronounced, and specific decrease in activated ERK1/2 [25].
• Thyrotropin-releasing hormone-induced spike and plateau in cytosolic free Ca2+ concentrations in pituitary cells. Relation to prolactin release [26].

Physical interactions of Prl

• Only when leptin was infused into the median eminence-arcuate nucleus complex was PRL secretion also stimulated, although its onset was 1 h behind that of LH [27].
• Interaction of prolactin (PRL) binding sites with PRL receptor antibodies in rat liver cells in suspension culture: effect of inhibitors of cellular functions [28].
• A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways [29].
• TRH stimulation appears to be coupled to PRL secretion, at least in part, by elevation of the concentration of Ca2+ free in the cytoplasm [( Ca2+]i) [30].
• The partially purified snake prolactin-like substance was also capable of displacing the binding of 125I-labelled ovine prolactin to snake kidney and large intestine membranes [31].

Enzymatic interactions of Prl

• Cathepsin D immuno-depletion abolished the capability of acini-conditioned medium to cleave the 23 kDa prolactin [32].

Co-localisations of Prl

• Vesicles containing non-secreted, internalized prolactin did not colocalize with DiI-LDL that had been chased into lysosomes but did transiently colocalize with internalized transferrin [33].

Regulatory relationships of Prl

• Both dopamine and U0126 enhance the nuclear localization of ERF, a MAPK-sensitive ETS repressor that inhibits prolactin promoter activity [25].
• Taken together, these data provide evidence for a role of multiple PKC isozymes in mediating both EGF and TRH stimulated PRL gene transcription [34].
• Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion [35].
• Neuropeptide Y suppresses prolactin secretion from rat anterior pituitary cells: evidence for interactions with dopamine through inhibitory coupling to calcium entry [36].
• Furthermore, we have shown for the first time that decidual PRL may act locally to activate the Jak2/Stat5 pathway and up-regulate important genes involved in decidual growth and placentation [37].

Other interactions of Prl

• The biphasic nature of TRH action on [Ca2+]i parallels the biphasic actions of TRH on 45Ca2+ fluxes and the biphasic release of PRL by GH cells in suspension [26].
• Polymerase chain reaction amplification of genomic DNA prepared from PRL-dependent and -independent cell lines suggests that this form of PRL-R results from a deletion in the PRL-R gene [1].
• Under these conditions, prolactin mRNA was only slightly (4-fold) increased by EGF [21].
• Surprisingly, prolactin stimulated a sustained activation of Raf-B, without activation of the MAP kinases ERK1 or -2 [20].
• Activation of Go-coupled dopamine D2 receptors inhibits ERK1/ERK2 in pituitary cells. A key step in the transcriptional suppression of the prolactin gene [25].

Analytical, diagnostic and therapeutic context of Prl

• Stats (signal transducers and activators of transcription) 3 and 5 DNA binding activities were induced by PRL/rPL-1 treatment of luteinized granulosa cells but only Stat 3 DNA binding was reduced by rottlerin [24].
• Supernatant was collected and analyzed for PRL content using radioimmunoassay [4].
• In this report, we have established by immunocytochemistry, RT-PCR, Western blot analysis, labeled amino acid incorporation and RIA that these cells express the rat PRL messenger RNA as well as synthesize and secrete PRL [37].
• We have also cloned by RT-PCR a 403-bp complementary DNA fragment whose sequence is identical with that of rat pituitary PRL [37].
• AP cells were incubated with peptides for 15 min, and medium PRL concentrations were determined by enzyme-linked immunosorbent assay [38].

References