Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice

Bôle‐Feysot, Christine

doi:10.1210/er.19.3.225

Cited by 760 publications

(884 citation statements)

References 118 publications

(171 reference statements)

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“…However, the short form mediates PRL actions in the rat corpus luteum [10], and its overexpression compensates for a partial loss of the long form in PRLR+/â knockout mice [21]. This, together with the activation of signaling pathways other than Jak/Stat by PRL [8], suggest that the short isoform has distinct functions.…”

Section: Discussionmentioning

confidence: 99%

“…The intracellular domain of the long isoform contains all the putative elements for activation of Jak/Stat signaling, whereas the truncated cytoplasmic domain of the short isoform lacks many of these [8]. It has been argued that the long isoform mediates most of PRL actions while the short isoform acts as a dominant negative [20].…”

Section: Discussionmentioning

confidence: 99%

“…PRL acts by binding to its receptor (PRLR), a member of the PRL-GH-cytokine receptor superfamily, and activating Jak/Stat signaling pathway [8]. In rats, PRLR exists as two isoforms, long (PRLR-L) and short (PRLR-S), whose expression varies in a tissue-specific manner [9].…”

Section: Introductionmentioning

confidence: 99%

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Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

Brandebourg

Bown

Ben‐Jonathan

2007

Biochemical and Biophysical Research Communications

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Prolactin (PRL) is recognized as a metabolic regulator during lactation, but little information exists on its actions in male adipose tissue. We examined whether PRL affects the expression of its receptors (PRLR), lipolysis and adipokine secretion in male rats. Both long and short PRLR isoforms were induced 40 to 50-fold during differentiation of epididymal preadipocytes, with a 10 fold higher expression of the long isoform. PRL upregulated both isoforms before and after differentiation. PRL suppressed lipolysis in epididymal explants and mature adipocytes in a dose-and time-dependent manner, which was reversed by a Jak2 inhibitor. PRL also inhibited leptin, but not adiponectin, release. We conclude that PRL inhibits lipolysis and leptin release by acting directly on adipocytes via interaction with either of its receptors and activation of a Jak2-dependent signaling pathway(s). This is the first demonstration of substantial effects of PRL on male adipocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

Brandebourg

Bown

Ben‐Jonathan

2007

Biochemical and Biophysical Research Communications

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“…Other metabolic abnormalities seen in prolactinomas include insulin resistance and dyslipidemia 5. In animal models, prolactin promotes accrual of visceral adipose tissue (VAT) 6. Prolactin receptor knockout mice have reduced overall and abdominal adipose tissue 7.…”

Section: Introductionmentioning

confidence: 99%

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Therkelsen

Abraham

Pedley

et al. 2016

JAHA

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BackgroundProlactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors.Methods and ResultsOur sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable‐adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5‐mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91–1.23, P=0.46). Some exceptions were of note. In women, for each 5‐mg/dL increment in prolactin, we observed increased odds of low high‐density lipoprotein cholesterol at follow‐up (odds ratio 1.50, 95% CI 1.18–1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5‐mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18–2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04–2.78, P=0.03).ConclusionsProlactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.

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“…In the latter, prolactin has been reported to act on water and electrolyte transport through the mucosa. 10,11 Numerous studies have provided evidence implicating a pathogenetic role of prolactin in breast cancer. On prolactin binding, the receptor exerts mitogenic effects involving various intracellular signaling cascades, such as JAK-STAT, ras-MAPK, and SHCGrb pathways.…”

mentioning

confidence: 99%

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases

et al. 2010

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The role of human prolactin and its receptor, the prolactin receptor, in colorectal cancer is largely unknown. Our study aimed to assess the prevalence of prolactin receptor expression, its association with clinicopathological variables, as well as its prognostic value, comparing results of primary tissues with those of corresponding metastases. In all, 373 primary colorectal cancer and 171 corresponding metastases were evaluated for prolactin receptor expression by immunohistochemistry using a tissue microarray technique. Immunoreactivity was semiquantitatively scored as either focal (o10% of tumor cells positive), moderate (10-50%), or extensive (450%). Prolactin receptor expression was related to clinicopathological parameters as well as patient outcome. To substantiate our findings, prolactin receptor expression was additionally assessed in HT-29 and SW-480 colorectal cancer cell lines using western blot. Prolactin receptor expression was observed in 360 out of 373 (97%) primary tumors, with 21 (6%) cases showing focal, 55 (15%) moderate, and 284 (76%) extensive expression, respectively. Extensive prolactin receptor expression was significantly associated with tumor size (P ¼ 0.002) and grade (Po0.001) as well as histological subtype (Po0.001). Somer's D coefficients for concordance of primary tumors with corresponding lymph node and distant metastases were D ¼ 0.719 (Po0.001) and D ¼ 0.535 (P ¼ 0.001), respectively. Extensive prolactin receptor expression was significantly associated with disease progression (P ¼ 0.03) and cancer-specific survival (P ¼ 0.04) in patients with highgrade cancers. In conclusion, prolactin receptor expression is common in colorectal cancer, with high concordance between primary tumors and corresponding metastases. In view of evolving targeted therapy concepts in colorectal cancer, widespread prolactin receptor expression may offer a therapeutic perspective in affected patients.

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Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice

Cited by 760 publications

References 118 publications

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases

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