Growth Hormone in Anorexia - First Lab Report Assignment PDF

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Growth Hormones Levels in Females with Anorexia Nervosa Compared to Healthy Controls Introduction Anorexia Nervosa (AN) is a psychiatric disorder characterised by elevations in growth hormone (GH) levels and decreased Insulin Growth Factor 1 (IGF-I) levels and is defined as a disorder of chronic malnutrition (Scacchi et. al., 2003). Under the strict fasting conditions of AN, the body relies on fibroblast growth factor 21 (FGF21) to induce the synthesis of ketone bodies in the presence of low glucose, (Mraz et. al., 2009, Fazeli et. al., 2009). It is understood that a disruption of the normal GH-IGH-I axis causes the high GH and low IGF-I pattern seen in AN patients (Fazeli et. al., 2009) and research behind these mechanisms indicate that there are many potential disruptions that could explain this phenomenon. However, the interaction between FGF21 and the GH-IGF-I axis in GH resistance is the focussed on in this paper.

In GH resistance, GH receptors at the level of the liver are unable to convert GH to its IGF-I protein product through the usual JAK/STAT pathway (Miller, 2013). In line with the somatomedin hypothesis, this plays into a negative feedback mechanism in which low IGF-I levels stimulate an increase in GH secretion, causing an excess of GH levels in individuals with this condition. In a study conducted by Fazeli et. al., AN patients (n=23) were measured for fasting FGF-21, and GH-AUC levels over a 12 hour period. Through their analysis it was concluded that a strong inverse correlation existed between FGF21 and IGF-I (R=-0.88), supporting the idea that FGF21 may play a role in the high GH and low IGF-I patterns seen in AN (2009).

AN is also known to affect other hormone pathways involved in growth, fat storage and hunger (Scacchi et. al., 2003). Leptin decreases appetite and stimulates energy expenditure and is thus elevated in disease characterised by increased fat storage, and low in disease characterised by low fat stores such as AN (Hebebrand et. al, 2007). Ghrelin induces feelings of hunger and stimulates the release of GH. Ghrelin is suppressed by sufficient intake of

nutrients and is therefore high in patients with AN who consume low calorie, low nutrient rich diets (Scacchi et. al., 2003).

The primary objective for this experiment was to measure the growth hormone levels in AN patients. To achieve this, an analysis of collected data was performed to further understand the response of GH to the condition AN.

Methods The AN patients were selected based on age (14), weight (39kg), height (160cm) and sex (female). Each patient (n=4) showed symptoms of amenorrhea and measured at low IGF-1 concentration levels (60ng/mL).

GH levels of each test subject were measured at 20 minute increments over a period of 24 hours to present a pulsatile GH profile for each test subject. Data was analysed to determine the baseline concentration, amplitude, frequency and overall mean of the data points for each subject’s profile in both the AN and control group. Baseline data points were defined as any value that fell below a quarter of the overall GH concentration mean for each subject ( x/4) and peaks were defined as anything that fell above this value.

An ANOVA was performed between subjects within the control group to determine whether there was a natural variability in the GH patterns of interest. The ANOVA comparing baseline & amplitude GH concentration values showed no significant difference between the control group subjects (p=ns). Thus, control group data could be considered normal and an appropriate control as any differences between the AN and control group could be attributed to the condition of AN itself.

To compare the mean GH concentration baselines of the AN and control group, a Welch’s ttest was selected as it does not assume equal variance for the two groups. A Welch’s t-test was also applied to compare GH concentration amplitude and the frequency of GH pulses in the AN and control group, as well as to compare the overall GH concentration mean.

Results were presented as a mean, standard error of the mean and as p-values. The software used to determine baseline, amplitude, and mean values was LabChart Reader and statistical analysis was performed using GraphPad Prism 8.

Results

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Figure 1: 24-hour GH secretory pattern comparison between AN female patients and female controls. A)

Basal GH concentration (ng/mL) measured for AN (n=4) and control group (n=4), **** p...