INT278567

Context Info Confidence 0.78 First Reported 2009 Last Reported 2010 Negated 2 Speculated 1 Reported most in Body Documents 2 Total Number 100 Disease Relevance 36.00 Pain Relevance 1.30

extracellular space (Kiss1) extracellular region (Kiss1) cytoplasm (Kiss1)

Anatomy Link Frequency neurons 26 gonadal 12 AVPV 4 gonads 3 neuronal 3 Kiss1 (Mus musculus)

Pain Link Frequency Relevance Heat substance P 11 99.96 agonist 10 95.40 addiction 198 93.96 Neuropeptide 495 93.72 Neurotransmitter 99 51.40 anesthesia 100 45.20 Inflammatory mediators 1 35.76 Central nervous system 2 5.00

Disease Link Frequency Relevance Heat Aids-related Complex 8019 100.00 Feminization 198 94.64 Eclampsia 1 77.20 Increased Venous Pressure Under Development 1 42.04 Endometriosis (extended) 1 40.80 Injury 198 35.68 INFLAMMATION 1 35.36 Reprotox - General 1 1 6.64 Overdose 99 5.00 Hypogonadotropic Hypogonadism 1 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Under conditions of high levels of circulating gonadal steroids, ARC Kiss1 expression decreases [10], thus ARC kisspeptin neurons are predicted to play a functional role in negative feedback regulation.

Gene_expression (expression) of Kiss1 in gonadal associated with aids-related complex

1) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.53 Pain Relevance 0

This would effectively clamp Kiss1 expression at a constant level, reinforcing the existence of a sensitive homeostatic regulatory mechanism.

Gene_expression (expression) of Kiss1

2) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.50 Pain Relevance 0

In contrast, the difference between sexes was not detected in hpg mice, consistent with our observations by ISH and ICC, further corroborating the loss of sexual dimorphism of kisspeptin expression in the AVPV of hpg mice.

Gene_expression (expression) of kisspeptin

3) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0 Pain Relevance 0

Finally, the change from the dense cellular staining in hpg ARC, corresponding to elevated Kiss1 gene expression, to a WT pattern of kisspeptin neuropil, suggests E2 restored kisspeptin distribution to a pattern found at low Kiss1 expression.

Gene_expression (expression) of Kiss1 in neuropil associated with aids-related complex

4) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.57 Pain Relevance 0.06

Similar to the ICC and ISH results, and in contrast to the results for the WT AVPV, there was no sexual dimorphism in ARC Kiss1 mRNA levels for either genotype (Fig. 6A, B).

Gene_expression (levels) of Kiss1 mRNA associated with aids-related complex

5) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.79 Pain Relevance 0

Since the levels of kisspeptin staining in the ARC were difficult to quantify by ICC, ISH was used to determine if the differences in ARC kisspeptin immunostaining patterns between the WT and hpg mice were associated with differences in Kiss1 gene expression.

Gene_expression (expression) of Kiss1 associated with aids-related complex

6) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.98 Pain Relevance 0

In the absence of gonadal sex steroid inhibition, ARC Kiss1 expression is markedly increased by P30 in both female and male hpg mice.

Gene_expression (expression) of Kiss1 in gonadal associated with aids-related complex

7) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.64 Pain Relevance 0

Kiss1 expression was measured based on the amount of total RNA extracted from the tissue which is known to have a linear correlation (r2?

Gene_expression (expression) of Kiss1

8) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.18 Pain Relevance 0

Exogenous estrogen increases Kiss1 expression and the number of detectable kisspeptin-immunoreactive neurons in the AVPV, which suggests the pubertal activity of the gonads in WT females likely underlies the greater developmental increases above that found in hpg females, and hpg males as well [9], [26].

Gene_expression (expression) of Kiss1 in gonads

9) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0 Pain Relevance 0

Our findings indicate that at the ages of normal pubertal maturation, increased kisspeptin is clearly detected in the hpg females and males, despite the absence of any appreciable exposure to gonadal sex steroid hormones.

Gene_expression (detected) of kisspeptin in gonadal

10) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.06 Pain Relevance 0

In contrast to the ARC, AVPV Kiss1 expression increases in response to gonadal steroids [10] and AVPV Kiss1 expression has also been shown to vary during the rodent estrus cycle, culminating with the highest levels of expression coincident with the ovulatory LH surge [9], [13], [14].

Gene_expression (expression) of Kiss1 in AVPV associated with aids-related complex

11) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.49 Pain Relevance 0

To next define the changes in Kiss1 gene expression in the AVPV during postnatal development in a hypogonadal background, RNA was collected from the AVPV of female and male WT and hpg mice at ages 10, 30, 45 and 60 days to analyze Kiss1 mRNA expression by real-time qRT-PCR (Fig. 3).

Gene_expression (expression) of Kiss1

12) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0 Pain Relevance 0

The complex maturation process that gates the pubertal transition appears to advance through ARC kisspeptin synthesis that is initially detected in both female and male hpg mice at 30 days, an effect difficult to detect in the intact WT as a result of negative feedback effects of sex steroid hormones.

Gene_expression (synthesis) of ARC kisspeptin associated with aids-related complex

13) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.46 Pain Relevance 0.05

We take these findings to indicate that Kiss1 expression is tightly regulated across the onset of puberty by both activational and repressive mechanisms.

Gene_expression (expression) of Kiss1

14) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.56 Pain Relevance 0

In contrast to the ARC, AVPV Kiss1 expression increases in response to gonadal steroids [10] and AVPV Kiss1 expression has also been shown to vary during the rodent estrus cycle, culminating with the highest levels of expression coincident with the ovulatory LH surge [9], [13], [14].

Gene_expression (expression) of Kiss1 in AVPV associated with aids-related complex

15) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.48 Pain Relevance 0

In this report, the role of E2 in peripubertal changes in kisspeptin expression was analyzed in the ARC and AVPV under controlled E2 conditions to reveal an increase in pubertal ARC Kiss1 mRNA expression and kisspeptin immunoreactivity in intact female rats between P21 and P26 [23].

Gene_expression (expression) of Kiss1 mRNA associated with aids-related complex

16) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.57 Pain Relevance 0

However, Kiss1 expression in the ARC of both hpg females and males increased significantly after day 10 and remained elevated through maturation (P<0.05; ANOVA, Neuman-Keuls post-hoc) (Fig. 6A, B).

Gene_expression (expression) of Kiss1 associated with aids-related complex

17) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.65 Pain Relevance 0

Accordingly, the hpg mouse provides an excellent model in which to study the onset and maturation of kisspeptin expression, without confounding developmental and trophic actions of gonadal sex steroids and other reproductive hormones.

Gene_expression (expression) of kisspeptin in gonadal

18) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.05 Pain Relevance 0

In the AVPV, Kiss1 expression increased only in WT females, not in WT males or in hpg mice.

Gene_expression (expression) of Kiss1

19) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0.32 Pain Relevance 0.03

To next define the changes in Kiss1 gene expression in the AVPV during postnatal development in a hypogonadal background, RNA was collected from the AVPV of female and male WT and hpg mice at ages 10, 30, 45 and 60 days to analyze Kiss1 mRNA expression by real-time qRT-PCR (Fig. 3).

Spec (analyze) Gene_expression (expression) of Kiss1 mRNA

20) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912854 Disease Relevance 0 Pain Relevance 0

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