Received December 4, 2001; Revised March 13, 2002; Accepted March 13, 2002. Author to whom all correspondence and reprint requests should be addressed: Prof. Sergio E. Recabarren, Universidad de Concepción, Casilla 537, Chillán, Chile. E-mail: srecabar@mail.udec.cl Pulsatile Leptin Secretion Is Independent of Luteinizing Hormone Secretion in Prepubertal Sheep Sergio E. Recabarren, 1 Alejandro Lobos, 1 Cecilia Vilches, 1 Paulina Muñoz, 1 and Teresa Sir-Petermann 2 1 Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Medicine, University of Concepción, Campus Chillán, Chile; and 2 Laboratory of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Universidad De Chile, Santiago, Chile Endocrine, vol. 17, no. 3, 175–184, April 2002 0969–711X/02/17:175–184/$12.50 © 2002 by Humana Press Inc. All rights of any nature whatsoever reserved. 175 Many studies have suggested that leptin modulates the gonadal axis. A synchronicity of luteinizing hor- mone (LH) and leptin has been described in humans, suggesting that leptin may modulate the episodic secre- tion of LH. The objective of this study was to establish whether episodic leptin secretion depends on the episodic LH secretion in prepubertal sheep. We used two different approaches. The first consisted of block- ing the release of LH using a long-acting LH-releasing hormone (LHRH) agonist and analyzing the episodic LH and leptin secretions. The second method stimu- lated the pituitary gland with pulses of LHRH and again LH and leptin secretions were analyzed. Spring-born 20-wk-old Suffolk ewe lambs (n = 5) received intra- muscularly a long-acting LHRH agonist (Decapeptyl ® ). Treatment was repeated at 24 and 28 wk of age. Con- trol lambs (n = 6) received the vehicle of Decapeptyl. Diurnal and nocturnal pulsatilities of LH and leptin were studied at 20 (before Decapeptyl injection), 26, and 30 wk. Blood samples were taken at 10-min inter- vals for 6 h, beginning at 10:00 AM (diurnal sampling) and at 10:00 PM (nocturnal sampling). In all samples, LH and leptin were measured by radioimmunoassay, and pulsatile hormone secretion characteristics were assessed by the CLUSTER program. To characterize further the synchronicity between LH and leptin pulses, LHRH (10 ng/kg body wt) was injected at 60-min inter- vals, six times, to another five 30-wk-old ewe lambs, for the same time period as the pulsatility study. In the control group, LH secretion did not change between lambs of 20 and 30 wk of age. In LHRH agonist–treated lambs, LH secretion diminished from 20 to 30 wk of age and was lower than in control lambs at 26 and 30 wk of age ( p < 0.05). The transversal mean (ng/[mL . 6 h]) of leptin concentrations was different between con- trol lambs of 20 wk of age and 26 and 30 wk of age ( p < 0.01). Contrary to the findings in LH secretion, in LHRH agonist–treated lambs, mean plasma leptin con- centrations did not decrease. Furthermore, the mean diurnal and nocturnal leptin concentrations and the pulse amplitude were higher at 26 and 30 wk than at 20 wk in LHRH agonist–treated lambs ( p < 0.05). There were no differences between diurnal and nocturnal parameters of leptin secretion in both groups. There was no synchronicity between LH and leptin pulses. LHRH pulses significantly increased plasma LH concen- trations, producing discernible LH pulses; however, leptin amplitude and leptin pulse frequency were not modified by the exogenous LHRH pulses, exhibiting no coincidence with LH pulses. The data suggest that pulsatile leptin secretion is independent of LH secre- tion in ewe lambs. Key Words: Luteinizing hormone; leptin; ewe lamb; copulsatility. Introduction The initiation of puberty in female sheep depends on a complex interplay between external and internal determi- nants whose final goal is the hypothalamus (1). The result of this neuroendocrine integration in the hypothalamus is the promotion of pulsatile luteinizing hormone–releasing hormone (LHRH) secretion, with an evident increase in pulse frequency. The increase in LHRH/luteinizing hormone (LH) secretion may be modulated by different metabolic signals of blood origin, which inform the LHRH pulse generator about the metabolic status of the growing female. One of these signals may be leptin. Leptin is a hormone produced mainly by adipocytes that has been postulated as a permissive metabolic signal in dif- ferent species, linking the energetic storage necessary for a successful pregnancy and the increase in LHRH secretion for the onset of puberty (2,3). In female rats, a minimal plasma leptin concentration of 700 pg/mL seems to be a threshold level for sexual maturation to progress (4). On the other hand, central administration of leptin in female rats under