Mathematical modelling of prolactin–receptor interaction and the corollary for prolactin receptor gene expression in skin

Soboleva, T. K.; Vetharaniam, I.; Nixon, A. J.; Montenegro, Renata de Lello; Pearson, A. J.; Sneyd, James

doi:10.1016/j.jtbi.2004.11.025

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…Thus, expression levels were low during telogen and early anagen but increased markedly by the 5th week of age, in accordance with previous studies that also report higher levels of PRLR transcripts during anagen (Craven et al 2001, Foitzik et al 2003. The lagged response of both full length and short form PRLR mRNAs in relation to circulating prolactin may reflect ligand-mediated receptor upregulation (Soboleva et al 2005) as has been reported in a number of organs including kidney, liver, mammary gland (Barash et al 1986) and adipose depots (Ling et al 2000), as well as skin (Nixon et al 2002). Assuming protein translation occurs, a functional role has yet to be ascribed for prolactin synthesised within the integument, but maintenance of tonic signalling during periods of low pituitary secretion has been postulated (Ben-Jonathan et al 1996).…”

Section: Discussionsupporting

confidence: 91%

“…Conversely, in a number of other species, hair follicle cycling is governed by seasonal changes to produce a summer and winter moult, and prolactin has been implicated as the principal endocrine regulator of this process (Martinet et al 1984, Loudon et al 1989, Dicks et al 1994, Pearson et al 1996, Thompson et al 1997. In recent years, it has become apparent that the method of prolactin administration and the resulting hormone profile are critical in determining the physiological response of hair follicles (McCloghry et al 1993, Soboleva et al 2005. The time at which prolactin is administered is also important, suggesting that follicles may be sensitive to prolactin at only some phases of the growth cycle.…”

Section: Introductionmentioning

confidence: 99%

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Prolactin delays hair regrowth in mice

Craven¹,

Nixon²,

Ashby³

et al. 2006

Journal of Endocrinology

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Mammalian hair growth is cyclic, with hair-producing follicles alternating between active (anagen) and quiescent (telogen) phases. The timing of hair cycles is advanced in prolactin receptor (PRLR) knockout mice, suggesting that prolactin has a role in regulating follicle cycling. In this study, the relationship between profiles of circulating prolactin and the first post-natal hair growth cycle was examined in female Balb/c mice. Prolactin was found to increase at 3 weeks of age, prior to the onset of anagen 1 week later. Expression of PRLR mRNA in skin increased fourfold during early anagen. This was followed by upregulation of prolactin mRNA, also expressed in the skin. Pharmacological suppression of pituitary prolactin advanced dorsal hair growth by 3 . 5 days. Normal hair cycling was restored by replacement with exogenous prolactin for 3 days. Increasing the duration of prolactin treatment further retarded entry into anagen. However, prolactin treatments, which began after follicles had entered anagen at 26 days of age, did not alter the subsequent progression of the hair cycle. Skin from PRLR-deficient mice grafted onto endocrine-normal hosts underwent more rapid hair cycling than comparable wild-type grafts, with reduced duration of the telogen phase. These experiments demonstrate that prolactin regulates the timing of hair growth cycles in mice via a direct effect on the skin, rather than solely via the modulation of other endocrine factors.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Prolactin delays hair regrowth in mice

Craven¹,

Nixon²,

Ashby³

et al. 2006

Journal of Endocrinology

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“…There is a negative correlation between prolactin and its receptors [42], suggesting that levels of prolactin in the cerebellum may increase after stress. Alternatively, changes in expression levels of PRLR may occur in response to changes of other hormones or cytokines that bind to PRLR.…”

Section: Discussionmentioning

confidence: 99%

“…After the recovery from stress the expression of PRLR returns to normal in cerebellum, but is down-regulated in hippocampus and up-regulated in prefrontal cortex. Negative correlation between prolactin and its receptors [42] suggests that levels of prolactin in the cerebellum may decrease after stress. Alternatively, changes in expression levels of PRLR may occur in response to changes of other hormones or cytokines that bind to PRLR.…”

Section: Discussionmentioning

confidence: 99%

Genomic and Epigenomic Responses to Chronic Stress Involve miRNA-Mediated Programming

et al. 2012

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Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function.

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“…The STAT5 sub-model shown in Figure 2B was developed by adapting the STAT3 model and substituting the receptor kinetics from Soboleva et al (2005), who modeled sequential binding of a ligand to its receptors but used an empirical representation of the JAK/ STAT pathway and did not include STAT and SOCS regulation. The STAT5 sub-model has 2 PRLR binding sequentially to PRL (a constant external input) to form a homodimer, which is subsequently phosphorylated (by JAK2) and then in turn phosphorylates STAT5 dimers.…”

mentioning

confidence: 99%

Cell survival signaling in the bovine mammary gland during the transition from lactation to involution

Singh

Vetharaniam

Dobson

et al. 2016

Journal of Dairy Science

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In dairy cows, mammary gland involution, and thus a decline in milk production, occurs following peak lactation. To examine the cell signaling pathways regulating involution of the mammary gland, signal transducer and activator of transcription factors (STAT5 and 3), suppressors of cytokine signaling (SOCS1-3 and CIS), insulin-like growth factors (IGF1 and 2), and protein kinase B (Akt) were examined. Mammary involution was induced by termination of milking, and alveolar tissue was collected from 52 nonpregnant, primiparous, mid-lactation Holstein-Friesian cows killed at 0, 6, 12, 18, 24, 36, 72, and 192h postmilking. Qualitative immunohistochemistry showed that activated (phosphorylated) STAT5-P was localized in nuclei of mammary epithelial cells at the early time points, with detection levels decreasing by 24h postmilking. In contrast, STAT3-P was barely detectable at the early time points, with detection levels increasing following longer postmilking periods. This was supported by Western analysis, which showed a decline in STAT5 and STAT5-P protein levels by 24h postmilking, no change in STAT3 levels, and an increase in STAT3-P protein (barely detectable at the early time points) by 72h postmilking. Quantitative real-time reverse transcription PCR analysis showed SOCS1 and SOCS3 mRNA increased by 72h postmilking compared with 6h postmilking. The SOCS2 mRNA remained unchanged across the time series, whereas CIS decreased by 18h postmilking and remained lower compared with that at 6h postmilking until 72h postmilking. The IGF1 mRNA increased by 192h postmilking, whereas IGF2 mRNA decreased by 18h postmilking compared with 6h postmilking. The IGFBP5 mRNA and protein levels of Akt and Akt-P remained unchanged over the time series. These results show that reciprocal activation of STAT5 and STAT3 occurs at the onset of mammary gland involution in the bovine, albeit at a slower rate than in rodents. Mathematical modeling of the pathways indicated that activated STAT3 could block the STAT5 pathway by upregulating SOCS3. The regulation of IGF1-Akt signaling suggests that by 192h postmilking in dairy cows, the involution process is still in the reversible phase, with quiescent mammary epithelial cells not yet in the senescent phase.

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Mathematical modelling of prolactin–receptor interaction and the corollary for prolactin receptor gene expression in skin

Cited by 5 publications

References 34 publications

Prolactin delays hair regrowth in mice

Prolactin delays hair regrowth in mice

Genomic and Epigenomic Responses to Chronic Stress Involve miRNA-Mediated Programming

Cell survival signaling in the bovine mammary gland during the transition from lactation to involution

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