INT2005

Context Info Confidence 0.70 First Reported 1979 Last Reported 2010 Negated 1 Speculated 2 Reported most in Body Documents 55 Total Number 57 Disease Relevance 21.40 Pain Relevance 13.44

cell proliferation (PRL) cytosol (PRL) extracellular region (PRL)

Anatomy Link Frequency plasma 20 pituitary 6 blood 4 thyroid 4 neurons 4 PRL (Homo sapiens)

Pain Link Frequency Relevance Heat MU agonist 2 99.98 narcan 38 99.76 Kinase C 16 99.76 Dynorphin 18 99.16 opiate 73 99.00 antagonist 323 98.98 gABA 208 98.96 Serotonin 520 98.84 Dopamine 1052 98.76 agonist 383 98.76

Disease Link Frequency Relevance Heat Systemic Lupus Erythematosus 103 99.84 Parkinson's Disease 3 99.70 Depression 330 99.50 Adenoma 228 99.36 Colorectal Cancer 95 99.28 Polycystic Ovary Syndrome 64 99.26 Cancer 306 99.24 Dystonia 1 99.24 Pituitary Cancer 139 98.76 Pain 84 98.64

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Most of the above mentioned medications lead to an increase in prolactin plasma concentration through an influence on prolactin secretion control, primarily removing inhibitor pathways or directly stimulating prolactin production by the lactotroph cells.

Positive_regulation (stimulating) of Gene_expression (production) of prolactin in lactotroph

1) Confidence 0.70 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.64 Pain Relevance 0.48

However, Schlienger et al showed that basal plasma levels of prolactin and delta prolactin response to TRH were increased in women on clomipramine but remained normal under maprotiline, in agreement with the different pharmacologic effect of these two classes of drugs, tricyclics mainly inhibiting serotonin, while tetracyclics rather norepinephrine recaptation (Schlienger et al 1980).

Positive_regulation (increased) of Gene_expression (levels) of prolactin in plasma associated with serotonin

2) Confidence 0.70 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.08 Pain Relevance 0.17

Histamine-induced prolactin production is mediated by dopaminergic as well as serotoninergic neurons, but other PRFs (eg, beta-endorphin, VIP, vasopressin or TRH) may be involved (Knigge 1990).

Positive_regulation (induced) of Gene_expression (production) of prolactin in neurons

3) Confidence 0.70 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.07 Pain Relevance 0.25

Histamine-induced prolactin production is mediated by dopaminergic as well as serotoninergic neurons, but other PRFs (eg, beta-endorphin, VIP, vasopressin or TRH) may be involved (Knigge 1990).

Positive_regulation (mediated) of Gene_expression (production) of prolactin in neurons

4) Confidence 0.70 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.13 Pain Relevance 0.26

Eldib et al in their unpublished study on 20 women with PCOS showed that LOD was associated with increased PRL levels by 7 folds two weeks after operation.

Positive_regulation (increased) of Gene_expression (levels) of PRL associated with polycystic ovary syndrome

5) Confidence 0.69 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1188073 Disease Relevance 0.78 Pain Relevance 0.05

Single nucleotide polymorphisms across the PRL extrapituitary promoter region have been associated with a relative overexpression of the PRL gene in SLE [14].

Positive_regulation (overexpression) of Gene_expression (overexpression) of PRL gene associated with systemic lupus erythematosus

6) Confidence 0.68 Published 2009 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2770548 Disease Relevance 0.92 Pain Relevance 0.28

1 may increase expression of PRL in endometrial stromal cells (ESC) [21], [22].

Spec (may) Positive_regulation (increase) of Gene_expression (expression) of PRL in stromal cells

7) Confidence 0.54 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2945765 Disease Relevance 0.15 Pain Relevance 0.11

Five patients had increased L PRL levels, but excess G PRL.

Positive_regulation (increased) of Gene_expression (levels) of PRL

8) Confidence 0.50 Published 2002 Journal Pituitary Section Abstract Doc Link 14558674 Disease Relevance 0.50 Pain Relevance 0.21

In response to TRH (200 micrograms, iv), PRL levels increased by 493 +/- 86% (mean +/- SE) over basal levels.

Positive_regulation (increased) of Gene_expression (levels) of PRL

9) Confidence 0.50 Published 1990 Journal J. Clin. Endocrinol. Metab. Section Abstract Doc Link 2118537 Disease Relevance 0.14 Pain Relevance 0.24

However, Schlienger et al showed that basal plasma levels of prolactin and delta prolactin response to TRH were increased in women on clomipramine but remained normal under maprotiline, in agreement with the different pharmacologic effect of these two classes of drugs, tricyclics mainly inhibiting serotonin, while tetracyclics rather norepinephrine recaptation (Schlienger et al 1980).

Positive_regulation (increased) of Gene_expression (response) of prolactin in plasma associated with serotonin

10) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.08 Pain Relevance 0.17

The net effect is an elevation of prolactin levels through increase in amplitude of prolactin bursts, release and storage (Halbreich et al 2003).

Positive_regulation (elevation) of Gene_expression (levels) of prolactin

11) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0 Pain Relevance 0.32

Treatment with either clomipramine or maprotiline in 17 patients with major depressive disorder and in healthy subjects increased significantly basal prolactin levels, that were also significantly higher in responders than in non-responders.

Positive_regulation (increased) of Gene_expression (levels) of prolactin associated with depression

12) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.16 Pain Relevance 0.19

A long list of other compounds may determine an increase in prolactin levels, including prokinetics, opiates, estrogens, anti-androgens, anti-hypertensive drugs, H2-receptor antagonists, anti-convulsivants and cholinomimetics.

Spec (determine) Positive_regulation (increase) of Gene_expression (levels) of prolactin associated with antagonist, hypertension and opiate

13) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Abstract Doc Link PMC2376090 Disease Relevance 0.63 Pain Relevance 0.33

These results suggest that in contrast to risperidone, where baseline prolactin levels were elevated 5.3-fold in female and 4.2-fold in male patients, baseline prolactin levels were not elevated after treatment with perospirone (Togo et al 2003).

Neg (not) Positive_regulation (elevated) of Gene_expression (levels) of prolactin

14) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.30 Pain Relevance 0.03

The robust increase in prolactin levels found in response to the GABA agonist alprazolam is not consistent with previous data on traditional benzodiazepines: Zemishlany et al reported that plasma prolactin levels increased by 100% two to eight hours after a single dose (3 mg) of alprazolam (Zemishlany et al 1990).

Positive_regulation (increase) of Gene_expression (levels) of prolactin in plasma associated with gaba and agonist

15) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0.20 Pain Relevance 0.49

-receptor binding, indirect simulation of prolactin synthesis through VIP and OT gene expression enhancement.

Positive_regulation (enhancement) of Gene_expression (synthesis) of prolactin

16) Confidence 0.50 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376090 Disease Relevance 0 Pain Relevance 0.39

This study establishes that (1) frequent uterine luminal fluid sampling is possible; (2) uterine luminal fluid volume decreases in the luteal phase; (3) uterine luminal fluid prolactin is detectable in vivo in women and its concentration increases in the luteal phase; and (4) cyclic human uterine luminal fluid prolactin levels differ from those in cynomolgus monkeys and from those anticipated from human in vitro studies.

Positive_regulation (increases) of Gene_expression (detectable) of prolactin in uterine

17) Confidence 0.50 Published 1988 Journal Am. J. Obstet. Gynecol. Section Abstract Doc Link 3407703 Disease Relevance 0 Pain Relevance 0.07

An elevated PRL level was common finding during and after operation with the peak PRL levels always occurring during surgery.

Positive_regulation (finding) of Gene_expression (levels) of PRL

18) Confidence 0.50 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1188073 Disease Relevance 0.63 Pain Relevance 0.25

When the DA antagonist metoclopramide was given in vivo to SLE patients, increased pituitary PRL responsiveness was demonstrated.

Positive_regulation (increased) of Gene_expression (responsiveness) of PRL in pituitary associated with dopamine, antagonist and systemic lupus erythematosus

19) Confidence 0.49 Published 2009 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2770548 Disease Relevance 1.15 Pain Relevance 0.39

This means that prolactin levels increase or decrease one month before a corresponding change in the number of active lesions is observed on MRI.

Positive_regulation (increase) of Gene_expression (levels) of prolactin

20) Confidence 0.49 Published 2006 Journal BMC Neurol Section Body Doc Link PMC1501038 Disease Relevance 0.12 Pain Relevance 0.08

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