Clinical Endocrinology (1998) 48 685–690 Rapid communication 685  1998 Blackwell Science Ltd The circadian rhythm of leptin is preserved in growth hormone deficient hypopituitary adults Eleni Kousta*, Alexandra Chrisoulidou*, Natasha J. Lawrence*, Kamal A. S. Al-Shoumer*, Kim H. Parker², Mark I. McCarthy* and Desmond G. Johnston* *Unit of Metabolic Medicine, Imperial College School of Medicine at St. Mary’s Hospital, London and ² Department for Biological and Medical Systems, Imperial College of Science, Technology and Medicine, London UK (Received 28 November 1997; returned for revision 24 December 1997; finally revised 13 January 1998; accepted 13 February 1998) Summary OBJECTIVE Leptin acts as a satiety factor in regulat- ing food intake and body homeostasis, but its regula- tion is not well defined. Specific leptin receptors have been found in the brain and it has been hypothesized that leptin production by adipose tissue is under neuroendocrine control. A circadian rhythm has been demonstrated with highest leptin levels between midnight and early morning hours. The possibility that hypopituitarism (or pituitary surgery  radiotherapy) abolishes this leptin rhythm was investigated by measuring serum leptin levels during a 24-h period in patients with impaired pituitary function. PATIENTS AND DESIGN Circulating leptin levels were measured hourly over 24-h in 14 hypopituitary patients (8 women and 6 men) using a sensitive and specific radioimmunoassay. Hypopituitarism was the consequence of pituitary tumors treated surgically and/or with radiotherapy. All patients were GH deficient and were receiving conventional replacement with cortisol (n ¼ 13), thyroxine (n ¼ 12) and desmopressin (n ¼ 4) but not with GH. RESULTS A significant diurnal variation in circulating leptin concentrations was observed in 13 of the 14 patients. The mean (SEM) leptin levels for 8 women were 51·9 (10·7) ng/ml and for 6 men 11·0 (2·0) mg/l. The overall lowest leptin levels (29·3  7·9 ng/ml) were observed at 0830 h after overnight fasting, rising gradually to maximum levels (43·0  9·8 ng/ml) at 0200 h declining thereafter towards fasting values. The mean (SEM) magnitude of circadian variation in absolute leptin levels from the calculated mean level for each patient was 5·6 (1·2) ng/ml (8·4  1·4 for women and 1·9  0·3 for men). The mean (SEM) of the ratio of the amplitude versus mean leptin levels over 24 h for each individual patient was 0·18 (0·02) (0·19  0·03 for women and 0·18  0·02 for men). CONCLUSIONS A circadian rhythm for leptin is gen- erally present in hypopituitary patients who had undergone pituitary surgery and/or radiotherapy, with the highest serum leptin levels being obtained between midnight and early morning hours. Although some patients had some residual pituitary activity, intact hypothalamic-pituitary function is not essential for leptin’s circadian rhythm. Leptin, the ob gene product, is a 16 kD plasma protein exclusively produced by adipose tissue (Zhang et al., 1994), which appears to play an important role in body weight homeostasis. In ob/ob mice, a mutation in the ob gene is associated with obesity, hyperphagia, hyperglycaemia and insulin resistance. When leptin was administered to leptin deficient obese mice, it resulted in decreased food intake, weight loss and increased energy expenditure (Pelleymounter et al., 1995; Halaas et al., 1995; Campfield et al., 1995). Plasma leptin levels are closely correlated with body fat: they are elevated in obese humans (Considine et al., 1996a) and decreased in states of severe malnutrition such as anorexia nervosa (Grispoon et al., 1996). Congenital leptin deficiency results in a phenotype with similarities to that seen in mice (Montague et al., 1997). Mutations of the leptin gene, though, do not seem to constitute a common cause of human obesity (Maffei et al., 1996). Although human obesity may not be, in most cases, a direct result of low leptin production, under- standing of its action and regulation may help in the development of new therapeutic strategies. Leptin receptors are distributed widely, including brain and many peripheral tissues (Considine et al., 1996b; Bray & York, 1997). It has been assumed that leptin provides a wide range of tissues with information about fat stores and acts as a signal to the central nervous system to induce the appropriate responses of food intake. It has been postulated that the effects of leptin in the brain may be through the reduction in the levels of Correspondence: Dr Eleni Kousta, Unit of Metabolic Medicine, St Mary’s Hospital, Norfolk Place, London W2 1PG, UK. Fax: þ44 171 886 6037; E-mail: e.kousta@ic.ac.uk