Endocrine Abstracts (2002) 3 P163

Gender variation in leptin circadian rhythm and pulsatility in adult growth hormone deficiency; effects of growth hormone replacement

HD White1, AM Ahmad1, R Guzder1, AM Wallace2, AA Syed1, J Thomas1, WD Fraser3 & JP Vora1

1Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, UK; 2Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, UK; 3Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, UK.

BACKGROUND: Healthy and Adult Growth Hormone Deficient (AGHD) women exhibit elevated leptin concentrations compared with men. AGHD is characterised by obesity and associated with increased leptin concentration and decreased leptin pulsatility, however the gender variation in rhythm and pulse parameters is yet to be defined. Following growth hormone replacement (GHR), leptin concentration decreases and pulsatility increases preceding a reduction in body fat mass (BFM).

OBJECTIVES: To determine the effect of gender on circadian and pulse parameters of leptin secretion in AGHD, and to determine gender variation in response of these parameters to GHR.

METHODS: Six men and six women, with severe AGHD, matched for age and BMI, were recruited. Plasma leptin was measured at half-hourly intervals for 24 hours, before and 1 month after initiation of GHR. Cosinor analysis was used to determine the circadian rhythm parameters, MESOR (rhythm-adjusted mean) and amplitude; and ULTRA algorithm used for pulse analysis. Body composition was measured using bioelectrical impedance. Local Ethical Committee approval was obtained.

RESULTS: BFM was higher in women than men at both visits (p=0.03), but there was no significant change in BFM in either gender following treatment. Women had higher 24-hour leptin mean concentration, MESOR, circadian amplitude and pulse amplitude, before and after GHR (p<0.01). Following treatment, the decrease in mean concentration and MESOR reached significance in women only (both p=0.04). Pulse frequency increased and duration decreased after GHR in both groups, without any significant gender difference.

CONCLUSIONS: Leptin concentration in women with AGHD is more responsive to the effect of GHR than in men. Decreases in leptin concentration and rhythm parameters have been shown to precede that of BFM. Therefore, it is possible that leptin, and indirectly GH, may have a regulatory role in body composition, perhaps with increased effect in women, resulting in future therapeutic implications.

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