Disease relevance of PRL

• Growth hormone but not prolactin concentrations in the fluid of bovine ovarian cysts are related to the cystic stage of luteinization [1].
• A method has been developed for the extraction from transformed Escherichia coli cells of methionyl bovine PRL (met-bPRL) in a relatively pure form [2].
• Somatostatin decreased the secretion of GH and PRL by pituitary tumor cells grown with or without T3 [3].
• Stimulation of the growth of quiescent NB2 node lymphoma cells in culture demonstrates that bPL and bovine PRL are equipotent in this bioassay [4].
• Body weight gain during 18 days of treatment with bovine prolactin (0.5 mg PRL/kg/day) was 27% greater than the value for corticosterone-treated hypophysectomized chickens, but bone growth was unaffected [5].

High impact information on PRL

• The site of methylation in the 3' end of prolactin mRNA was determined [6].
• An in vitro methylation system was developed in which bovine prolactin mRNA, synthesized in vitro with T7 RNA polymerase, was accurately methylated in a HeLa cell nuclear extract [6].
• Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene [7].
• In mammotrophs, heavy PRL labeling was observed over secretory granule matrices (including the immature matrices at the trans Golgi surface) and also over Golgi cisternae [8].
• All somatotrophs and mammotrophs were heavily positive for GH and PRL, respectively, and were found to contain small amounts of the other hormone as well, which, however, was almost completely absent from granules, and was more concentrated in the Golgi complex, admixed with the predominant hormone [8].

Chemical compound and disease context of PRL

• Among all other cows, including those with dystocia alone, adjusted yields were increased by heavier calves (P < .07, Y60), high plasma PRL (P < .025, Y60) and below average plasma E1 (P < .025, Y200) [9].
• Secondly, plasma PRL responses to the intravenous (i.v.) injection of bPP extract (0.5 eq./head), PrRP [3.59 mug/kg body weight (BW)], TRH (1 mug/kg BW), and a dopamine receptor antagonist (sulpiride, 0.1 mg/kg BW), were examined in calves [10].
• Among photoperiod exposures, prolactin released into blood after injection of 33 micrograms/100 kg body weight of thyrotropin-releasing hormone paralleled the changes described for basal conditions [11].
• Serum concentrations of prolactin were reduced in heat-stressed heifers fed infected seed and both heat stress and infected seed decreased total cholesterol [12].
• In this study, we evaluated the effects of several hormones (i.e. growth hormone, prolactin, vitamin D3, luteinizing hormone, oxytocin) on the phagocytosis and intracellular survival of Mycobacterium avium ss. paratuberculosis within bovine peripheral blood monocytes [13].

Biological context of PRL

• These data support the concept that greater responsiveness and sensitivity to PRL during transition to lactation may be associated with an increase in subsequent milk yield [14].
• Prior to PRL treatment, SDPP animals had greater lymphocyte proliferation and neutrophil chemotaxis relative to LDPP animals [15].
• PRL mRNA expression was less in the regressed stage (days 19-21 after ovulation) than in the other stages [16].
• Blocking experiments with anti-prolactin (PRL) antibody led to a 60% decrease in cell growth [17].
• While PRL is known to activate Jak2-Stat5 (signal transducer and activator of transcription 5) signaling pathway, the mechanism by which cell proliferation is stimulated is less known [18].

Anatomical context of PRL

• During the dry period, PRL and PRL-R mRNA were analyzed biweekly in plasma and lymphocytes, respectively [14].
• These results demonstrate that the bovine mammary gland is responsive to exogenous PRL during early lactation [19].
• Incorporation of [(3)H]thymidine into DNA was not affected by frequent milking or PRL treatment; however, analysis of autoradiograms revealed that stromal cell proliferation was greater in 4x cows [19].
• Gram-negative bacterial lipopolysaccharide (LPS) and the Gram-positive bacterial lipoteichoic acid (LTA) substantially upregulated transcriptional expression driven by the Saa3 promoter in bovine mammary epithelial cells by 18.5-fold and 12.5-fold, respectively, whereas the lactogenic hormone, prolactin (PRL) stimulated a 3.5-fold increase [20].
• We also measured the levels of PRL mRNA in cultured luteal cells and luteal endothelial cells [16].

Associations of PRL with chemical compounds

• The minimal Saa3 promoter fragment that retained responsiveness to LPS, LTA, or PRL was 352 bp in size [20].
• Concentrations of GH, PRL, estrogens (E(2)), progesterone (P(4)) and testosterone (T) were measured in follicular and cystic fluids [1].
• Exposure of cultured luteal cells obtained from mid-stage CL (days 8-12) to bovine PRL (100, 200 ng/ml) for 24 hr did not affect P4 and PGF2alpha production by the cells [16].
• Furthermore, the effect of PRL on progesterone (P4) and prostaglandin (PG) F2alpha production by cultured bovine luteal cells was examined [16].
• Dex inhibition was reversed by the higher concentration of PRL added to cells [18].

Physical interactions of PRL

• In addition, CPE co-precipitated at pH 5.8 with purified prolactin and with insulin, which homophillically self-aggregate yet are structurally distinct from N-POMC [21].
• Prolactin receptors were shown to be abundant in the rabbit mammary glands but no specific binding sites for 125I-labelled GH have been found in membranes isolated from mammary glands of pregnant or lactating rabbits [22].
• However, bovine placental lactogen is known to bind prolactin receptors in rabbit mammary gland [23].

Enzymatic interactions of PRL

• We have previously characterized the phosphorylation of bovine PRL and wish to determine whether a similar kinase activity phosphorylates bovine GH [24].

Regulatory relationships of PRL

• These studies define the basis of cellular trafficking of PRLR isoforms and increase our understanding of control of target cell responsiveness by PRL [25].
• The inhibitory effects of the trans-10, cis-12 CLA isomer on PRL-induced IDH1 expression accumulation were confirmed by quantitative real time PCR and western-blotting analysis [26].
• Two-dimensional immunoblot analyses of colostrum and milk from healthy cows, as well as conditioned medium from PRL or LPS stimulated bovine mammary epithelial cells confirmed the differential production and secretion of M-SAA3 while other SAA isoforms were not detected [27].
• Plasma concentrations of PRL increased (P less than .01) with age (r = +0.938) in control heifers while plasma TSH and GH were not significantly related to age [28].
• We hypothesized that this effect is due to increased growth of mammary cells in response to enhanced prolactin signaling to influence the insulin-like growth factor (IGF) axis [29].

Other interactions of PRL

• Bovine serum amyloid A3 gene structure and promoter analysis: Induced transcriptional expression by bacterial components and the hormone prolactin [20].
• Short day photoperiod was associated with reduced PRL, whereas milk yield and expression of PRL-R mRNA in lymphocytes and mammary tissue were increased [14].
• Bovine corpus luteum is an extrapituitary site of prolactin production [16].
• In competition studies for [125I]16K PRL binding, 16K PRL was most potent, while little displacement was observed with high concentrations of 23K PRLs, growth hormones, and basic fibroblast growth factor [30].
• Prolactin, growth hormone, and chorionic somatomammotropin (placental lactogen) constitute a set of related polypeptides believed to derive from a common evolutionary ancestor protein [31].

Analytical, diagnostic and therapeutic context of PRL

• Semiquantitative RT-PCR analysis revealed that the mRNAs for PRL and its two receptors, l- and s-PRLR, were expressed in all luteal stages examined [16].
• On tissues treated with 250 ng/mL of leptin, GH and PRL mRNA, as well as protein content, were estimated by reverse transcription-PCR and Western immunoblotting, respectively [32].
• 16K PRL was generated by the proteolysis of rat 23K PRL with a particulate fraction from rat mammary gland homogenates and purified by gel filtration [30].
• PRL in the serum was determined by radioimmunoassay (RIA) [33].
• Using the membrane-bound receptor and bovine serum, the serum level of PRL was determined by radioreceptor assay (RRA) [33].

References