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Clinical Chemistry 45: 1235-1239, 1999;
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(Clinical Chemistry. 1999;45:1235-1239.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

Gender Differences in Diurnal Growth Hormone and Epinephrine Values in Young Adults during Ambulation

Britt Edén Engströma, F. Anders Karlsson and Leif Wide

Department of Medical Sciences, University Hospital, S-751 85 Uppsala, Sweden.
a Address correspondence to this author at: Department of Medical Sciences, Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden. Fax 46 18 55 36 01; e-mail Britt.Eden_Engstrom{at}medicin.uu.se


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: In the present study, the impact of gender, oral contraceptives, and ambulation on serum growth hormone (GH) and urinary catecholamines was examined in healthy young adults.

Methods: Twenty-one medical student volunteers—7 men, 7 women, and 7 women taking oral contraceptives—were investigated. Serum samples were drawn every second hour during a 24-h period. At 0800 the first morning, serum samples were drawn while subjects were in the ambulatory state; the next morning, serum samples were drawn at 0800 while the subjects were still resting in bed.

Results: During the daytime, GH concentrations were sevenfold higher in the women than in the men, a difference larger than described previously. During the night, there was no gender difference. In the morning, ambulatory GH concentrations were 28-fold higher in the women than in the men, whereas supine GH concentrations were only 4.6-fold higher in the women than in the men. Daytime urinary output of epinephrine was lower in the women than in the men, whereas there was no difference at night. Women using estrogen-containing oral contraceptives had lower epinephrine and higher GH values than women not taking oral contraceptives. In women, morning GH concentrations were higher in the ambulatory than in the resting state, whereas they were lower in the ambulatory state than in the resting state in men.

Conclusions: The secretion of GH and epinephrine is gender-dependent and differs during the daytime in a reciprocal manner, with higher GH and lower epinephrine in women than in men. Oral contraceptives appear to further increase such differences. It seems likely that the data reflect a gender difference in the utilization of substrates for energy production.© 1999 American Association for Clinical Chemistry


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Growth hormone (GH) secretion is augmented under catabolic conditions of fasting and stress and by certain amino acids (1). GH secretion is also increased during physical activity (2)(3). In contrast, GH release is inhibited by food intake and an increase in blood glucose, high serum free fatty acids, and obesity (1)(4). GH plays a major role in the metabolism and storage of body lipids (1). Marked effects on the body composition, with a breakdown of adipose tissue, are seen after treatment of GH-deficient adults, males being more sensitive than females (5). Nocturnal GH concentrations correlate with ketone body concentrations in terms of timing and magnitude (6). Several observations have indicated that there are interactions between GH and epinephrine. One major metabolic effect of epinephrine is a rapid mobilization of substrates from lipid deposits in adipose tissue and from glycogen in the liver and skeletal muscle. Epinephrine acts in synergy with GH to increase lipolysis (7)(8)(9). Among healthy adults, men have a higher output of epinephrine than women in response to physical activity (2)(3)(10) or hypoglycemia (11)(12)(13).

The aim of the present study was to examine the impact of gender and oral contraceptives (OCs) on GH and epinephrine secretion during 24 h. In addition, GH was analyzed in the ambulatory as well as in the resting state in the morning after an overnight fast. Healthy young men, women with normal menstrual cycles, and women taking OCs were included in the study.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
study subjects
Twenty-one medical student volunteers were included in the study—7 men (mean age, 25.8 years; range, 23–29 years), 7 women with normal menstrual cycles (mean age, 24.1 years; range, 22–28 years), and 7 women taking OCs (mean age, 23 years; range, 20–29 years). The body mass index was 21.3 (range, 19.8–23.7) in the men, 23.5 (range, 17.6–27.3) in the women not taking OCs, and 23.8 (range, 21.3–25.9) in the women taking OCs. The subjects were healthy and were not taking any medication (OCs) that could influence the hormone concentrations. In the women, the samples were taken at random times during the menstrual cycle.

Among the seven women taking OCs, three took a combination of 20–30 µg of ethinyl-estradiol and 150 µg of desogestrel and four took a combination of 30–40 µg of ethinyl-estradiol and 50–150 µg of levonorgestrel. All women on hormonal contraceptives had a free interval of 7 days.

study design
Serum samples were drawn in the ambulatory state and analyzed for GH at 0800 when the subjects first came to the hospital after an overnight fast. The subjects returned to the hospital at 1800 for the beginning of a 24-h GH profile. Samples were taken every second hour until 1600 the next day. The subjects remained in bed from ~2300 and when samples were taken at 0800 the next morning after an overnight fast. During the day, subjects were free to walk around. Urine was collected in 4-h periods for the assay of epinephrine and norepinephrine. All subjects gave informed consent. The study was approved by the Ethics Committee of the Medical Faculty of Uppsala University.

methods
GH in 50 µL of serum (s-GH, 22 kDa) was measured with a noncompetitive sandwich time-resolved fluoroimmunoassay (AutoDELFIATM hGH kit; Wallac Oy) specific for the pituitary 22-kDa GH isoform. The results were expressed in mIU/L, using the first international reference preparation of GH (80/505) as a reference standard. The minimum detection limit was 0.009 mIU/L. The within- and between-assay CVs were 1.1% and 2.3%, respectively.

The urinary contents of epinephrine and norepinephrine were determined by HPLC (14)(15).

statistics
The serum GH values were transformed into logarithms before analysis. The serum GH values are presented as geometric means (± SD). The ± SD values for GH were derived from the antilogarithm of the mean (i.e., the geometric mean) plus or minus 1 SD of the log-transformed data. The urinary values are presented as the means (± SD). Five summary statistics have been calculated from the GH serial data: mean values during the daytime, the nighttime, and 24 h, respectively, and maximal peak and nadir values. Statistical analyses were based on these values. When the ANOVA factorial overall test was significant (P <0.05) for differences among groups, the unpaired two-tailed Student t-test was used as a posthoc test. This method controls the total experiment-wise error rate at 5% for the situation when three groups are being compared (16). Statistical comparisons within the same group were made on paired observations, using the two-tailed Student t-test.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
24-h gh profiles
The women showed sevenfold higher daytime serum GH concentrations than the men (Fig. 1 ). During the night, there was no significant difference between the sexes. GH concentrations during the 24-h study period were 4.7-fold higher in the women than in the men (Table 1 and Fig. 1 ). The mean maximum values differed by twofold and the mean nadir values differed by threefold between men and women.



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  		Figure 1. Serum GH concentrations (geometric mean ± SE) in seven men, seven women, and seven women taking OCs during a 24-h period in which the subjects were resting in bed between 2300 and 0800.

{square}, men; {circ}, women not taking OCs; •, women taking OCs.


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  		Table 1. Serum GH concentrations during 24 h in seven men, seven women, and seven women taking OCs, ages 20–29 years.1

The daytime and 24-h serum GH concentrations for the seven women taking OCs were nearly 13-fold higher and 6.5-fold higher than in the men, respectively (Table 1Up ). The 24-h GH profiles in the two groups of women were similar (Fig. 1Up ).

influence of ambulation on gh values
Serum GH concentrations in the seven women not taking OCs were 28-fold higher at 0800 in the ambulatory state and 4.6-fold higher at 0800 in the supine state than in the men (Table 1Up ). In the men, the values were threefold lower in the ambulatory state compared with the resting state, whereas they were twofold higher in both groups of women. Both groups of women had similar concentrations in both the ambulatory and the resting states.

urinary outputs of epinephrine and norepinephrine over 24 h
A gender difference was seen in the 24-h pattern of the epinephrine output. The men had a higher output than the women during the day, whereas the outputs were similar at night (Table 2 ). There was also a difference between the two groups of women; the women taking OCs had lower values during the day than those not taking OCs, whereas the values were similar during the night. The mean epinephrine value in the urine during the 24-h period was higher in the men than in the women not taking OCs. The mean value in the women taking OCs was even lower. There was no difference between the groups in the diurnal pattern of the urinary outputs of norepinephrine.


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  		Table 2. Mean urinary output (± SD) of epinephrine and norepinephrine during daytime, nighttime, and during 24 h in seven men, seven women, and seven women taking OCs, ages 20–29 years.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In the present investigation of young adults, we observed a larger gender difference than had been described previously, with women having sevenfold higher serum GH concentrations than men during the day and nearly fivefold higher GH concentrations over the 24-h period. In other studies that also used highly sensitive GH immunoassays, the GH concentrations over 24 h were 1.4- to 2.9-fold higher in women than in men when GH was measured every 10 to 20 min (17)(18)(19). The ages of the individuals in those studies were 20–47, 30–55, and 43–53 years, respectively, and they came to the hospital the day before the study and were free to move around from the first sampling in the morning (18)(19) or after 1 h in bed (17). Potentially, the large gender difference in our study reflects the younger age of the subjects and sampling during routine daily activity. The difference in the GH secretion pattern over the 24-h period was readily observed despite blood samples being drawn only every second hour. Furthermore, it has been shown that with increasing sampling intervals, the typical pulsatile pattern of GH becomes distorted, but that the estimate of the cumulative secretion is unaffected (20). The circadian rhythmicity of GH secretion is well known. Recently, cosinor analysis of 24-h GH serum concentration profiles revealed an increased nocturnal GH-secretory release that was larger in men than in women (18). This is in accordance with the present study: we observed approximately eight- and twofold increases in the mean nighttime GH values of men and women, respectively.

Ambulation in the mornings influenced the fasting 0800 GH in different ways in the men than in the women: in the men, the values were threefold lower in the ambulatory state compared with the resting state, whereas they were twofold higher in both groups of women. The low value in the men in the ambulatory state was in agreement with our previous study (21).

In the present study, the urinary epinephrine output over 24 h was higher in men than in women, in accordance with observations in the literature (22)(23). A similar gender difference has also been reported for plasma catecholamines (24)(25). In another study, females displayed greater lipid utilization and less carbohydrate and protein metabolism during exercise than men, who showed greater muscle glycogen utilization. The higher epinephrine values in males during exercise might account for this difference in glycogen utilization (3). A new observation is that the women taking OCs had lower urinary epinephrine than the women not taking OCs and much lower values than the men.

Activation of ß-adrenoceptors in the brain has been shown to inhibit the secretion of GH via an increase in the output of somatostatin (26). Therefore, the increased epinephrine values during ambulation during the day might cause a larger inhibition of GH release in men.

In conclusion, we found that daytime GH concentrations were sevenfold higher in young women than in young men, a difference larger than that reported previously. Furthermore, epinephrine values were lower in women than in men, suggesting a reciprocal relationship between GH and epinephrine during the day. This finding was more pronounced in women taking OCs. These observations might reflect a gender difference in the proportions of GH- and epinephrine-dependent energy production. The marked gender differences in GH values and urinary catecholamines suggest that establishment of sex-specific references ranges for these analytes should be considered.


   Acknowledgments
 
This study was supported by grants from the Medical Research Council. We thank Maria Söderling, Christer Bengtsson, and Mats Flodin for expert technical assistance, Frank Niklasson for valuable advice on measurements of catecholamines, and Lars Berglund for valuable advice on statistics.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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