The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients, 2010, Shishioh-Ikejima et al

[forestglip]

The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients

Spoiler: Authors

Shishioh-Ikejima, Nobue; Ogawa, Tokiko; Yamaguti, Kouzi; Watanabe, Yasuyoshi; Kuratsune, Hirohiko; Kiyama, Hiroshi

Background
Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS) has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (α-MSH) have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased α-MSH plasma levels may also occur in CFS patients. We therefore examined α-MSH levels in CFS patients.

Methods
Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of α-MSH, adrenocorticotropic hormone (ACTH), serum cortisol and dehydroepiandrosterone sulfate (DHEA-S). Mean levels of α-MSH were compared between the CFS and control groups using Welch'sttest.

Results
The mean plasma α-MSH concentration in the CFS group (17.9 ± 1.0 pg/mL) was significantly higher than that in healthy controls (14.5 ± 1.0 pg/mL, p = 0.02). However, there was a wide range of values in the CFS group. The factors correlated with the plasma α-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma α-MSH values (p = 0.04, rs= -0.28), but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively).

The CFS patients were divided into two groups: patients diagnosed for ≤ 5 years' duration, and those diagnosed for 5-10 years' duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean α-MSH concentration in the ≤ 5 years group was 20.8 ± 1.2 pg/mL, which was significantly higher than that in the healthy controls (p < 0.01). There was no significant difference between the 5-10 year group (15.6 ± 1.4 pg/mL) and the healthy controls.

Conclusions
CFS patients with a disease duration of ≤ 5 years had significantly higher levels of α-MSH in their peripheral blood. α-MSH could be a potent biological marker for the diagnosis of CFS, at least during the first 5 years after onset of the disease.

Web | DOI | PMC | PDF | BMC Neurology | Open Access

 

[forestglip]

This is an older study. Posting because of a possible connection to increased prolactin response in ME/CFS. I'll put those details on the prolactin response thread. [Edit: link]

Fukuda criteria ME/CFS and age/sex-matched healthy controls:

The study subjects included 55 patients with CFS (35.4 ± 1.1 years old) and 30 age-sex-matched healthy controls who did not complain of feeling fatigued and had no illness, as healthy controls (36.1 ± 1.6 years old).

The CFS patients were diagnosed using the clinical criteria proposed by Fukuda (1994) [1]

Alpha-melanocyte-stimulating hormone (a-MSH) was increased in the ME/CFS group:

The mean plasma concentration of α-MSH in the CFS group was 17.9 ± 1.0 pg/mL, which was higher than that in the healthy group (14.5 ± 1.0 pg/mL, p = 0.02).

When splitting by duration, a-MSH was high in the patients with duration of illness less than 5 years, but not in those with duration 5-10 years:

CFS patients were divided into two groups: a shorter CFS duration group (from 6-60 months) and a longer CFS duration group (from 61-120 months). As shown in Figure 3, the shorter duration group had significantly higher levels of α-MSH than the healthy controls (p = 0.002, by one-way ANOVA; p < 0.01 by Tukey's test).

 

[Axel]

I don’t know if it’s related, but for the first four or five years, all I did was sleep.

 

[forestglip]

I don’t know if it’s related, but for the first four or five years, all I did was sleep.

You might be thinking of melatonin. This hormone is related to melanin, the pigment in skin and hair. From Wikipedia:

[α-Melanocyte-stimulating hormone] is the most important of the melanocyte-stimulating hormones (MSHs) (also known as melanotropins) in stimulating melanogenesis, a process that in mammals (including humans) is responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, sexual activity, and protection against ischemia and reperfusion injury.[1]

 

[forestglip]

They included some discussion of prior findings about increased prolactin response, and suggested that prolonged stress might increase a-MSH, based on a rat study where stress increased pituitary release of a-MSH. They also say that it's possible the source of the increased a-MSH in this study might be blood cells and not pituitary.

Dopaminergic neurons located in A14 (the hypothalamic periventricular region) project their axons to the intermediate lobe and suppress melanotroph activity via dopamine production. [...] Furthermore, removal of the pituitary gland resulted in suppression of the stress-induced increase of the plasma α-MSH, suggesting that the chronic stress-induced increase of α-MSH originated from the pituitary gland.

Intriguingly, Sharpe et al. demonstrated an increase in prolactin response in CFS, and suggested the possibility that CFS patients could have an abnormal dopamine neurotransmission [20]. [...] It thus seems likely that the increase in circulating α-MSH in CFS patients originates from the pituitary gland in response to persistent and prolonged stress.

However, some human studies have reported that some blood cells in patients with sepsis and some inflammatory diseases secrete α-MSH [21], and the possibility that α-MSH is released by some blood cells in CFS patients following prolonged stimulation cannot be ruled out.

 

[Axel]

Oups, yes, I was actually thinking of melatonin.
There’s some research on MSH and sleep, but it seems only beginning. However, its role in several metabolic pathways appears to be very interesting.

I’m also thinking of another study which showed higher levels of circulating cytokines during the first five years, tending to decrease thereafter in ME/CFS patients. Could there be a link?